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Stimuli-Responsive Molecularly Imprinted Polymers for Drug Delivery: A Review
Abstract
Molecular imprinting is an efficient technique for introducing regions with a highly specific molecular arrangement into a polymeric matrix. The first example of a molecularly imprinted polymer (MIP) was reported half a century ago; however, the use of molecular imprinting has become a well established practical tool only in the last decade. Recently, MIPs are widely used, for example, in chromatographic applications or enzyme antibody mimics. MIPs have also been used in biological applications such as drug delivery systems (DDS), and they have also been successfully applied as excipients in controlled delivery systems. Their huge potential could bring about intelligent drug release; this refers to the release, in a predictable way, of therapeutic agents in response to specific environmental stimuli (the presence of another molecule, pH changes, temperature, etc.). This review is focused on particular intelligent devices of this type that exhibit selective recognition (traps for toxic molecules) and release (of drugs in order to prolong the duration of pharmacological action) in response to specific stimuli. The "stimuli-responsive molecularly imprinted polymers" reviewed in this paper are expected to contribute significantly to the exploration and development of new generations of intelligent and self-regulated drug delivery systems.
... The obtained MIPs possess tailored cavities resembling the original template in terms of size, shape and orientation [36]. Regarding drug delivery, due to the intermolecular interactions like hydrogen bonds, dipole-dipole and ionic interactions between the template molecule and polymer functional groups, these cavities are capable of enhancing the NPs loading capacity, improving drug stability, solubility and adjusting the drug release kinetics [4,37,38]. An intelligent or smart drug release is the anticipated release of a therapeutic agent on-demand. ...
... This feature is highly suitable for DDS as it allows the drugs to be released only upon a particular change in the environment (Figure 1) [35] such as heat, pH changes, light, electric or magnetic fields, enzymes, reduction and ultrasound waves [8,29]. The combination of stimuli-sensitivity and imprinting technology potentially leads to a high loading capacity of the template by imprinting, while the response to the external stimuli modulates the affinity of the polymeric network for the template molecule, providing the regulatory or switching capability of the loading/release processes [37]. ...
... The main advantages of MIPs in comparison with biomolecules such as antibodies and biologic receptors are their relatively high stability over various conditions and low cost [37]. MIPs have stable spatial structure and long-lasting shelf life that can be up to several years at room temperature [38] and exceptional physical robustness and stability against tough conditions, including highly acidic and basic pH, temperature fluctuation, organic solvents and mechanical and thermal pressures [36], [39,40]. ...
Cancer therapy is still a huge challenge, as especially chemotherapy shows several drawbacks like low specificity to tumor cells, rapid elimination of drugs, high toxicity and lack of aqueous solubility. The combination of molecular imprinting technology with magnetic
nanoparticles provides a new class of smart hybrids, i.e., magnetic molecularly imprinted polymers (MMIPs) to overcome limitations in current cancer therapy. The application of these complexes is
gaining more interest in therapy, due to their favorable properties, namely, the ability to be guided and to generate slight hyperthermia with an appropriate external magnetic field, alongside the high
selectivity and loading capacity of imprinted polymers toward a template molecule. In cancer therapy, using the MMIPs as smart-drug-delivery robots can be a promising alternative to conventional direct administered chemotherapy, aiming to enhance drug accumulation/penetration into the tumors while fewer side effects on the other organs. Overview: In this review, we state the
necessity of further studies to translate the anticancer drug-delivery systems into clinical applications with high efficiency. This work relates to the latest state of MMIPs as smart-drugdelivery systems aiming to be used in chemotherapy. The application of computational modeling toward selecting the optimum imprinting interaction partners is stated. The preparation methods employed in these works are summarized and their attainment in drug-loading capacity, release
behavior and cytotoxicity toward cancer cells in the manner of in vitro and in vivo studies are stated. As an essential issue toward the development of a body-friendly system, the biocompatibility and
toxicity of the developed drug-delivery systems are discussed. We conclude with the promising perspectives in this emerging field. Areas covered: Last ten years of publications (till June 2020) in magnetic molecularly imprinted polymeric nanoparticles for application as smart-drug-delivery systems in chemotherapy.
... The overall process yields highly crosslinked polymeric materials, which preserve a binding pocket after the removal of the template, as illustrated in Figure 1. The resulting molecularly imprinted polymeric materials have been explored in different applications, including solid phase extraction [9], catalysis [10], separation [11], sensing [12], and drug delivery [13], since their preparation methods are relatively straightforward, robust, and reliable. In addition, the numerous commercially available or synthetically accessible monomers enable the fabrication of materials that bear the potential to replace the utilization of natural receptors in many of these applications. ...
... Each method has unique characteristics and various advantages and disadvantages, as summarized in Table 1. The resulting molecularly imprinted polymeric materials have been explored in different applications, including solid phase extraction [9], catalysis [10], separation [11], sensing [12], and drug delivery [13], since their preparation methods are relatively straightforward, robust, and reliable. In addition, the numerous commercially available or synthetically accessible monomers enable the fabrication of materials that bear the potential to replace the utilization of natural receptors in many of these applications. ...
Recent years have witnessed increased attention to the use of droplet-based microfluidics as a tool for the fabrication of microparticles due to this method’s ability to exploit fluid mechanics to create materials with a narrow range of sizes. In addition, this approach offers a controllable way to configure the composition of the resulting micro/nanomaterials. To date, molecularly imprinted polymers (MIPs) in particle form have been prepared using various polymerization methods for several applications in biology and chemistry. However, the traditional approach, that is, the production of microparticles through grinding and sieving, generally leads to poor control over particle size and distribution. Droplet-based microfluidics offers an attractive alternative for the fabrication of molecularly imprinted microparticles. This mini-review aims to present recent examples highlighting the application of droplet-based microfluidics to fabricate molecularly imprinted polymeric particles for applications in the chemical and biomedical sciences.
... With self-assembly MIPs, the FM, T, XL and porogen are pre-mixed and allowed to self-associate prior to polymerisation. To optimise the formulation, pre-synthetic approaches such as virtual imprinting [32][33][34], semi-empirical calculations [11], thermodynamic studies [35,36], spectroscopic (NMR [37,38], UV-VIS [39,40] and FTIR [41]) analyses, chemometric methods [42] and combinatorial screening [33,43,44] have been extensively employed. Commercially available FMs are commonly utilised, except in cases where specialty monomers are required. ...
Molecularly imprinted polymers (MIPs) for benzylpiperazine (BZP, 1), an illicit designer drug, were developed by using both self-assembly and semi-covalent approaches. From an array of potential functional monomers (FMs) and using a combination of pre-synthetic interaction studies (by molecular modelling and NMR analysis) and binding assays, the highest performing self-assembly 1-MIPs were confirmed to result from methacrylic acid (7) as FM, ethylene glycol dimethacrylate (EGDMA) or trimethylolpropane trimethacrylate (TRIM) as crosslinkers and chloroform as the porogen and rebinding solvent at template (T): FM ratios of 1:1 and 1:2, giving imprinting factors (IF) 3 to 7. The semi-covalent 1-MIPs were designed using benzylpiperazine (4-vinylphenyl) carbamate (16) as the template–monomer adduct in combination with either EDGMA or TRIM. Our comparative analysis showed the semi-covalent polymers to have a stronger affinity for 1 (significantly lower Kd values and higher IFs) and faster uptake than the self-assembly systems. Both approaches have comparable cross-reactivity: marginal to low against cocaine (17) and morphine (18) and high against ephedrine (19) and phenylpiperazine (20). They also have comparable selectivity: highly selective towards 1 against 17, moderate against 18 and non-selective against 19. EGDMA-based self-assembly MIPs displayed a greater imprinting effect (higher IFs and NIP-to-MIP Kd ratios) than TRIM-based MIPs, while the TRIM-based semi-covalent MIP outperformed its EGDMA-based equivalent. By virtue of its modest selectivity against the test illicit drugs, 1-MIPs could potentially be used as a dummy MIP for the broad-based capture and enrichment of illicit drug blends for subsequent laboratory analysis.
... One of the major qualities necessary for the optimal design of therapeutic agents for oral administration is the release of an imprinted molecule in response to changes in the acidity of the surrounding medium (Ciurba et al. 2021b). Additionally, its excellent alternatives in the area of DDS are alginate MIP as pH-sensitive polymer hydrogels with such a polymeric network that is able to take or donate protons at a given pH, through a volume phase transition from a collapsed state to an extended one (Puoci et al. 2008;Kurczewska 2022). ...
In this study, alginates, as the most versatile polymers, were employed to construct selective and effective molecular imprinted polymer (MIP) as a solid phase extraction adsorber for the estimation of tenoxicam (TNX) in pharmaceutical formulations. Based on the non-covalent approach, the polymerization reaction was performed with sodium alginate as a monomer, calcium chloride as a crosslinking reagent, and TNX as a template. The formed polymer was characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). The distribution ratio results showed that the particle formed ranges were less than 100 nm. To evaluate binding capacity, batch binding assays were utilized, and the results were monitored using UV–Vis spectroscopy at 369 nm. The drug delivery of the imprinted surface was studied in different acidic media that mimic the gastric medium, intestine and blood plasma. The results show that the best way to deliver drugs is in the acidic environment of the stomach.
... mass% that can be attributed transition pyrolysis of hydrocarbons formed. Also, Figure 3c) the thermal properties of the polymeric matrix (PCL) prevailed, occurring a weight loss at 400 °C of 10% corresponding to the degradation of Tr, and an increase of temperature degradation at 650°C (Puoci et al., 2008). Through the melting enthalpy obtained by DSC chart of the polymer matrix PCL and PCL-TCs. ...
Efeito antibacteriano e liberação de tetraciclina de matrizes de poli(Ɛ-caprolactona) obtidas por polimerização de iodo Efecto antibacteriano y liberación de tetraciclinas de matrices de poli(Ɛ-caprolactona) obtenidas por polimerización con yodo Abstract The development of devices to controlled the release of drugs are in constant technological innovation. The aim is to improve the release of drugs on target areas. Poly (ε-caprolactone) (PCL) has been widely investigated because of degradation rate, biocompatibility, availability, no toxicity, cost and good adhesion to a large number of drugs. Thus, in the present study was associated polymer PCL with antibiotics tetracycline as local delivery system. PCL was obtained by ring-opening polymerization of monomer Ɛ-caprolactone (Ɛ-CL). The samples were characterized by fourier transformed infrared (FTIR), differential scanning calorimetric (DSC), thermogravimetric analyses (TGA) and X-ray diffraction analysis (X-rays). Likewise, was investigated antimicrobial activity against gram-positive bacteria (S. aureus) and gram-negative bacteria (E. coli, P. mirabilis, P. aeruginosa and K. pneumoniae). According to the results, the antibiotics tetracycline has been successfully incorporated to PCL matrices. They release tetracycline in the ideal rates and shows antibacterial activity. So, this material has a potential to been used in implants for drug release.
... MIPs have many advantages, including high selectivity, mechanical and chemical stability, low cost and easy preparation, and a long storage life. Over the past decades, these polymers have been successfully used in different fields [10][11][12][13][14][15] such as chemical sensors [16][17][18][19][20], enzyme mimicking catalysis [21][22][23], intelligent drug delivery [24][25][26][27], etc. In particular, MIPs have been extensively employed as the adsorbents of the solid phase extraction (SPE) for the selective extraction of a target compound and structural analogues from the complex matrices, such as natural products [28][29][30][31][32]. ...
Molecularly imprinted polymers (MIPs) were synthesized and applied for the selective extraction of oblongifolin C (OC) from fruit extracts of Garcinia yunnanensis Hu. A series of experiments and computational approaches were employed to improve the efficiency of screening for optimal MIP systems in the study. The molar ratio (1:4) was chosen at last based on the comparison of the binding energy of the complexes between the template (OC) and functional monomers using density functional theory (DFT) at the RI-PBE-D3-gCP/def2-TZVP level of theory. The binding characterization and the molecular recognition mechanism of MIPs were further explained using the molecular modeling method and NMR and IR spectra data. The reusability of this approach was demonstrated in over 20 batch rebinding experiments. 140.5 mg of OC (>95% purity) was obtained from the 5 g extracts with 2 g of MIPs with the best binding properties through gradient elution program from 35% to 70% methanol-water solution. At the same time, another structural analog, 46.5 mg of guttiferone K (GK) (>88% purity), was also obtained by the gradient elution procedure. Our results showed that the structural analogs could be separated from the crude extracts by the molecularly imprinted solid-phase extraction (MISPE) using a gradient elution procedure for the first time.
... [151,152] Among these approaches, molecular imprinting is one of the most fascinating one, which employs enantiomer molecules as asymmetric templates to encode chiral information inside a bulk matrix. [102,153] Molecularly imprinted polymers (MIPs) were the first examples of the molecular imprinting technology, and they have been widely used for mimicking biologically active sites inside the polymer matrices. For example, MIPs were first studied and used as chiral adsorbent for chiral chromatography in 1978. ...
The development of porous materials has been one of the most fascinating research topics in the frame of a wide variety of applications ranging from chemical analysis to separation and catalysis. Among the huge amount of different porous materials, nanoporous metals are one of the most interesting candidates because of their outstanding properties such as a high surface area, a large pore volume and a high accessibility for guest molecules which have to diffuse into the internal matrix where catalytically active sites are located. In order to synthesize such materials, a templating approach, including hard and soft templating is typically used to generate uniform porous structures, depending on the shape of the templates. In the present dissertation thesis, the elaboration of various porous metal electrodes via a soft templating approach and their potential applications in the field of enantioselective analysis, synthesis and separation are discussed. Several chiral imprinted metals such as platinum and nickel with a significantly increased internal electroactive surface area are studied. Subsequently, these chiral imprinted mesoporous metals can be used to improve the electrochemical performance with respect to several tasks, including electrochemical synthesis of chiral compounds, chiral separation and actuation, which are important for pharmaceutical applications. The first part of the present work is devoted to the elaboration of chiral imprinted metals for asymmetric synthesis. The prepared electrode surfaces show a surprisingly high selectivity in terms of chiral synthesis when they are combined with the concept of pulsed electrochemistry. The second part of the manuscript is dedicated to their use for the separation of racemic mixtures with the opportunity to fine-tune the separation efficiency by applying a potential to the metal matrix in order to adjust the electrostatic interactions between the chiral compounds and the designer surfaces. Under the most suitable conditions, complete baseline separation of both enantiomers can be observed. The third part of this thesis deals with chiral detection, for which a hybrid film of chiral imprinted Pt and polypyrrole is used as a selective actuator under bipolar electrochemical conditions. The synergistic properties of both materials, wireless actuation and chiral recognition, have been successfully combined for wireless chiral analysis. Apart from the design and application of chiral mesoporous metal films, the last chapter is dedicted to the elaboration of hierarchically structured metals containing macro- and mesoporous features, obtained by using simultaneously hard and soft templating approaches for electrocatalytic oxygen evolution in basic media. Multiporous nickel nanosheets were prepared via a two-step electrodeposition process in the presence of silica beads and surfactant as templates to control the macro- and mesoporous structure, respectively. The resulting synergistic effect of combined macroporous and mesoporous cavities allows fine tuning structural properties, electrocatalytic performance and stability for water splitting applications. In conclusion, our findings open interesting perspectives for development of new porous materials, which are of potential interest for various applications, such as chiral analysis, asymmetric synthesis, chemical separation, as well as energy conversion and storage.
... Among various stimuli-responsive MIPs that have been developed, photoresponsive MIMs have attracted particular attention, since light is a stimulus that can be introduced immediately and conveyed with high accuracy in exact amounts [128]. Fang et al. [100] described the first method to achieve MIMs containing an azo group with stimuli-responsive properties, both thermo-and photoresponsive, in aqueous media by utilising an acetonitrile-soluble azo functional monomer with a pyridine group (i.e., 4-((4-methacryloyloxy)phenylazo)pyridine [MAzoPy]), a crosslinker, a template and polyNIPAAm (PNIPAAm) brushes for surface grafting via surface-initiated ATRPP. ...
Molecularly imprinted polymers (MIPs) are specific crosslinked polymers that exhibit binding sites for template molecules. MIPs have been developed in various application areas of biology and chemistry; however, MIPs have some problems, including an irregular material shape. In recent years, studies have been conducted to overcome this drawback, with the synthesis of uniform microsphere MIPs or molecularly imprinted microspheres (MIMs). The polymer microsphere is limited to a minimum size of 5 nm and a molecular weight of 10,000 Da. This review describes the methods used to produce MIMs, such as precipitation polymerisation, controlled/‘Living’ radical precipitation polymerisation (CRPP), Pickering emulsion polymerisation and suspension polymerisation. In addition, some green chemistry aspects and future perspectives will also be given.
... Stimuli-responsive molecularly imprinted polymers (MIPs) have been explored widely using several types of external stimuli such as pH, light, and heat [24][25][26][27][28][29]. In a previous study, we had successfully fabricated mild-gas-stimuli-responsive MIP particles [30]. ...
Molecular recognition materials possessing switchable recognition characteristics have immense potential for use in a wide range of applications. Herein, core-shell-type molecularly imprinted polymer (MIP) particles, containing protein recognition nanocavities with mild-gas-stimuli responsiveness, are synthesized via emulsifier-free emulsion polymerization, followed by seeded polymerization in an aqueous medium using 2-diethylaminoethyl methacrylate as a functional monomer with CO2- and N2-responsive interaction sites. Based on the gas responsiveness of the interaction sites in the recognition nanocavities, the affinity of the MIP particles toward a target protein could be regulated successfully by introducing mild gas stimuli. These gas-stimuli-responsive nanomaterials could find use in areas such as affinity chromatography and reusable sensing materials due to their low toxicity, low cost, and high usability.
... MIPs are applied in separation and purification techniques where chromatography is one of their most traditional applications [21,22]. Their applications are extended to chemical sensors and biosensors [23], catalysis [24] and drug delivery [25]. MIP is considered a promising technique for the recognition of biological and chemical molecules [26,27] including amino acids and proteins [6,8], pollutants [10] and drugs [12]. ...
... Nanomaterials find applications in precision agriculture, smart plant protection, nutrition, and management practices in farms due to small size, high surface to volume ratio, and unique optical properties (Ghormade et al. 2011). There are many types of nanomaterials which can be used in agriculture as carbon based including single-walled and multi-walled carbon nanotubes (SWCNT/MWCNT); metal-and metal oxide-based dendrimers (nano-sized polymers) as aluminum (Al), copper (Cu), gold (Au), silver (Ag), silica (Si), and zinc (Zn) nanoparticles, magnetized iron (Fe) nanoparticles, zinc oxide (ZnO), titanium dioxide (TiO 2 ), and cerium oxide (Ce 2 O 3 ); or biocomposite nanomaterials (EPA 2007;Nair et al. 2010) or nanoparticles like ceramics, semiconductor, quantum dots, polymers (synthetic or natural), dendrimers, and emulsions (Puoci et al. 2008). ...
Nanotechnology has opened up new avenues in precision and sustainable agriculture by offering more efficient fertilizers and pesticides. The effects of use of these nanomaterials include increased seed germination, length of root-shoot, and biomass of the seedlings along with enhancement of the physiological parameters that enhance nitrogen metabolism and photosynthetic activity in many crop plants. They also provide many other benefits as reducing the amount of chemical used and increasing the absorption of nutrients from the soil, hence reducing the agricultural inputs. Nanotechnology holds the promises controlled release of agrochemicals as well as targeted delivery of several macromolecules. This technology may be used to make nanoscale sensors for monitoring the soil quality as well as nutritional status of agricultural field. Precise and on-demand application of nanopesticides or nanofertilizers can enhance the productivity and prove protection against several pests without harming the environment.
... Recently, a series of reports have been published describing the use of nanoMIPs as drug carriers for insulin, (R)-thalidomide, carbazole derivatives, quercetin, and paclitaxel anti-cancer drugs [30,[165][166][167][168]. The drug release was achieved using either photo-, thermo-, or pH-responsive stimuli [169][170][171][172][173]. For imaging applications nanoMIPs can be easily functionalized either with quantum dots or fluorescent dyes [139,174,175]. ...
Materials that can mimic the molecular recognition-based functions found in biology are a significant goal for science and technology. Molecular imprinting is a technology that addresses this challenge by providing polymeric materials with antibody-like recognition characteristics. Recently, significant progress has been achieved in solving many of the practical problems traditionally associated with molecularly imprinted polymers (MIPs), such as difficulties with imprinting of proteins, poor compatibility with aqueous environments, template leakage, and the presence of heterogeneous populations of binding sites in the polymers that contribute to high levels of non-specific binding. This success is closely related to the technology-driven shift in MIP research from traditional bulk polymer formats into the nanomaterial domain. The aim of this article is to throw light on recent developments in this field and to present a critical discussion of the current state of molecular imprinting and its potential in real world applications.
... [10][11][12] The imprinted polymers are widely used in various application areas, such as separation sciences and purification, sensors and biosensors, catalysis and drug delivery. [13][14][15][16][17][18][19][20] The ion-imprinted polymers (IIP) have been synthesized using different methods like bulk, [21,22] suspension, [23,24] precipitation, [25] sol-gel [26] and hydrothermal assisted surface imprinting. [27] Despite the outstanding advantages of IIPs as high selectivity and recognition ability, low costing of synthesis and high physical/chemical stability, they have also some disadvantages like low binding capacity due to highly cross-linked rigid structures and the difficulties in the removal of the target analyte from the polymeric structure. ...
A novel Zn(II) ions imprinted poly (2-hydroxyethyl Methacrylate-N-methacryloyl-(L)-histidine methyl ester) poly(HEMAH) surface plasmon resonance (SPR) nanosensor were designed for detection of Zn(II) ions in aqueous solution and artificial plasma providing a low cost, rapid and reliable results compared to other techniques such as atomic absorption spectroscopy, inductively coupled plasma-mass spectrometer, X-ray fluorescence with synchrotron radiation. Zn(II) ions imprinted nanofilm on the SPR chip surface was synthesized by bulk polymerization. Characterization of Zn(II) ions imprinted nanosensor was performed by contact angle measurement, atomic force microscopy (AFM), ellipsometry and Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR). Designed nanosensor was applied for selective detection of Zn(II) ions in aqueous solution within the range of 0.5–1.0 µg/mL. The limit of detection (LOD) and limit of quantification (LOQ) were calculated as 0.19 and 0.64 ng/mL, respectively. Association kinetics analysis, Scatchard, Langmuir, Freundlich, Langmuir–Freundlich, Tempkin and Dubinin-Radushkevich isotherms were analyzed to the experimental data in order to identify the adsorption behavior. The selectivity of the SPR nanosensor was examined by using competitive metal ions such as Cd(II), Cu(II), Pb(II), and Fe(II). To evaluate the imprinting effect of Zn(II) ions imprinted (MIP) and non-imprinted (NIP) nanosensor was also prepared as the control. Repeatability of the response signal was tested by four times adsorption–desorption–regeneration cycle.
... Consequently, the resultant polymer able to recognizes and rebinds selectively the template or other molecules that are chemically related to the template [24,25]. This technique is used in many applications such as selectivity recognation and seperation [26][27][28][29], drug delivery systems [30][31], catalysis [32,33] sensor technology [34,35]. In addition, ion imprinted polymers (IIPs) have been used for the selective removal of metal ions from different matrices [36][37][38][39][40][41][42][43][44][45][46][47]. ...
... There are some issues with usual MIPs, including low binding capacity, poor site availability, and slow binding kinetic. The various uses of some special co-functional monomers like N-isopropylacrylamide, acrylic acid, and azobenzene monomers, in molecular imprinting beside suitable election of amounts of cross-linkers allows responsive MIPs to be obtained with different stimuli such as temperature, pH, and light [22]. Azobenzene and its derivatives have been widely utilized as the functional monomer of MIPs owing to the unique properties of the azobenzene chromophore, which include its high stability and photomechanical virtues, rapid, and reversible photo-isomerization [23,24]. ...
This study introduced a developed approach for the use of polyester dendrimer during the imprinting process to raise the number of recognized sites in the polymer matrix and improve its identification ability. Photo‐responsive molecular imprinting polymers were synthesized on modified magnetic nano‐particles involving polyester dendrimer which uses the reactivity between allyl glycidyl ether and acrylic acid for the high‐yielding assembly by surface polymerization. The photo responsive molecular imprinting polymers were constructed using methylprednisoloneacetate as the template, water‐soluble azobenzene involving 5‐[(4, 3‐(methacryloyloxy) phenyl) diazenyl] dihydroxy aniline as the novel functional monomer, and ethylene glycol dimethacrylate as the cross‐linker. Through the evaluation of a series of features of spectroscopic and nano‐structural, this sorbent showed excellent selective adsorption, recognition for the template, and provided a highly selective and sensitive strategy for determining the methylprednisoloneacetate in real and pharmaceutical samples. In addition, this sorbent according to good photo‐responsive features and specific affinity to methylprednisoloneacetate with high recognition ability, represented higher binding capacity, a more extensive specific area, and faster mass transfer rate than its corresponding surface molecularly imprinted polymer.
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... Among various CSPs, those that are manufactured based on molecularly imprinted polymers (MIPs) displayed remarkably higher efficiency compared to the other previously mentioned types concerning the lower cost, higher affinity, selectivity, and ease of preparation [24,25]. These important features have expanded the utility of MIPs not only in the enantiomeric chiral purification but also in some biotechnical applications including drug delivery systems [26,27], biosensors [28][29][30], and artificial antibodies [31,32]. ...
... Chemical structure Reference Dithiodipropionic acid [62] Dithiobis(succinimidylpropionate) [63] Cystamine bisacrylamide [64] Cystamine [65] 2-(pyridyldithio)-ethylamine [66,67] N-succinimidyl 3-(2-Pyridyldithio)propionate ...
Currently, to overcome low therapeutic efficiencies and side effects of anticancer agents, the study of drug carrier based on polymers have been consistently investigated. Although the traditional drug carrier based on polymers displayed an excellent result and significant progress, there has been a problem with the side effect and low therapeutic efficiency because of the premature drug release before reached to the targeted region by the low stability in blood stream and sustained drug release. In this review article, to improve the problem of inefficient drug release, methods were suggested, which can maximize the therapeutic efficiency by increasing the stability in the blood stream and triggering drug release at the target site by introducing a stimuli-responsive substance to the non-toxic and biocompatible natural polymer chitosan. © 2018 The Korean Society of Industrial and Engineering Chemistry. All rights reserved.
... Stronger and highly selective interactions between drug and polymer result in enhanced loading and prolonged release [14], potential for design of stimulus responsive MIPs, ability to shield drugs from enzymatic degradation [15], controlled and constant drug release useful in ocular delivery [16]. MIPs can function as controlled drug delivery matrices wherein the rate and time of drug release can be tuned according to the binding affinity between the drug and the matrix. ...
Molecularly imprinted polymers are crosslinked macromolecular structures endowed with specific binding cavities for a template moiety. Their selectivity and stability against harsh conditions coupled with their easy and economical fabrication have fueled various research endeavors in a myriad of applications, such as chromatographic separation, solid phase extraction, sensors, catalysts, and drug delivery. The chapter focuses on the fabrication aspects of molecularly imprinted polymers and gives an insight into the components and various methods employed for their production. Limitations of conventional methods have driven the development of novel techniques to generate water-compatible molecularly imprinted polymers and protein imprinted polymers. The chapter further showcases recent advances in the fabrication of molecularly imprinted polymers, such as use of supercritical fluid, epitope imprinting, and surface imprinting to overcome the drawbacks associated with conventional methods of molecularly imprinted polymer fabrication.
... Molecular imprinting today is a versatile and promising technique, which is able to recognize small molecules, biomolecules and macromolecules including amino acids and proteins (Bossi et al., 2007;Scorrano et al., 2011), pollutants (Pichon and Chapuis-Hugon, 2008), pharmaceuticals and food (Baggiani et al., 2007;Puoci et al., 2007). In addition, molecular imprinted materials can be easily applied to separation and purification, chemical sensors, catalysis and drug delivery (Puoci et al., 2008) systems. ...
... Molecules of similar shape, size, and functional group will fit perfectly into the binding sites created during the synthesis of the materials. Molecularly imprinted polymers (MIPs) constitute a promising material that offers many applications for the separation sciences and purification [26], drug delivery [27], biological antibodies receptors systems [28], and catalysis [29]. This is due to their ability to recognize various molecules like amino acids and proteins [30], nucleotide derivatives [31], pollutants [32], drugs, and food [33]. ...
... The response of nanoparticle drug delivery systems to these internal stimuli allows tumor-specific release of the payload. External stimuli can also be applied for additional specificity in tumor-targeted drug delivery (Puoci, Iemma, & Picci, 2008). In the following subsections, we focus on recent developments in the design of nanoparticle-based stimuli-responsive systems that are able to control drug release in response to external (temperature, magnetic field, ultrasound, light, or electric pulses) or internal (pH, enzyme concentration, or redox gradients) stimuli. ...
Effective and safe delivery of anticancer agents is among the major challenges in cancer therapy. The majority of anticancer agents are toxic to normal cells, have poor bioavailability, and lack in vivo stability. Recent advancements in nanotechnology provide safe and efficient drug delivery systems for successful delivery of anticancer agents via nanoparticles. The physicochemical and functional properties of the nanoparticle vary for each of these anticancer agents, including chemotherapeutics, nucleic acid-based therapeutics, small molecule inhibitors, and photodynamic agents. The characteristics of the anticancer agents influence the design and development of nanoparticle carriers. This review focuses on strategies of nanoparticle-based drug delivery for various anticancer agents. Recent advancements in the field are also highlighted, with suitable examples from our own research efforts and from the literature.
... The response of nanoparticle drug delivery systems to these internal stimuli allows tumor-specific release of the payload. External stimuli can also be applied for additional specificity in tumor-targeted drug delivery (Puoci, Iemma, & Picci, 2008). In the following subsections, we focus on recent developments in the design of nanoparticle-based stimuli-responsive systems that are able to control drug release in response to external (temperature, magnetic field, ultrasound, light, or electric pulses) or internal (pH, enzyme concentration, or redox gradients) stimuli. ...
Cancer is a daunting global problem confronting the world's population. The most frequent therapeutic approaches include surgery, chemotherapy, radiotherapy, and more recently immunotherapy. In the case of chemotherapy, patients ultimately develop resistance to both single and multiple chemotherapeutic agents, which can culminate in metastatic disease which is a major cause of patient death from solid tumors. Chemoresistance, a primary cause of treatment failure, is attributed to multiple factors including decreased drug accumulation, reduced drug-target interactions, increased populations of cancer stem cells, enhanced autophagy activity, and reduced apoptosis in cancer cells. Reprogramming tumor cells to undergo drug-induced apoptosis provides a promising and powerful strategy for treating resistant and recurrent neoplastic diseases. This can be achieved by downregulating dysregulated antiapoptotic factors or activation of proapoptotic factors in tumor cells. A major target of dysregulation in cancer cells that can occur during chemoresistance involves altered expression of Bcl-2 family members. Bcl-2 antiapoptotic molecules (Bcl-2, Bcl-xL, and Mcl-1) are frequently upregulated in acquired chemoresistant cancer cells, which block drug-induced apoptosis. We presently overview the potential role of Bcl-2 antiapoptotic proteins in the development of cancer chemoresistance and overview the clinical approaches that use Bcl-2 inhibitors to restore cell death in chemoresistant and recurrent tumors.
... To date, many researches have been published developing imprinting protocols in different fields such as chiral separation [4], solid-phase extraction (SPE) [5], chemical catalysis [6], and drug delivery systems [7]. Most of the developed protocols in the molecular imprinting technology are produced in organic solvents [8,9] due to their lower polarity and hydrogen bonding ability compared to aqueous media. ...
In the present study, a molecularly imprinted polymer (MIP) was prepared for Furosemide drug as template molecule in H2O/THF (1:1 v/v) medium using Fe³⁺ as metal ion mediator. Acrylic acid, acrylamide, and N,N′-methylenebis(acrylamide) were used as functional monomer, comonomer, and cross-linking agent, respectively. Different binding and selectivity parameters of the prepared system were studied and compared with the corresponding metal ion-free MIP and non-imprinted polymer (NIP). The presence of the metal ion during pre-assembly step showed a significant influence on the imprinting ability of the resulting polymeric network due to its strong interactions with the template molecule and the functional monomer. Besides, structural, thermal, and morphological characterizations of the prepared system were investigated. In the final step, the in vitro release study of Furosemide from the synthesized polymers was carried out in pH = 7.41 phosphate-buffered saline solution at 37 °C. Results indicated that the Fe³⁺-mediated MIP (Fe-MIP) has larger drug loading capacity and higher amount of drug release at its equilibrium state. Moreover, according to the drug release profiles, the drug release rate of the Fe-MIP is more controlled than that of the MIP and the NIP, especially at the early stages of release.
... MIPs have many advantages, including high selectivity, mechanical and chemical stability, low cost and easy preparation, and a long storage life. Over the past decades, these polymers have been successfully used in different fields [10][11][12][13][14][15] such as chemical sensors [16][17][18][19][20], enzyme mimicking catalysis [21][22][23], intelligent drug delivery [24][25][26][27], etc. In particular, MIPs have been extensively employed as the adsorbents of the solid phase extraction (SPE) for the selective extraction of target compounds and structural analogues from complex matrices, such as natural products [28][29][30][31][32]. ...
Molecularly imprinted polymers (MIPs) were synthesized and applied for the selective extraction of oblongifolin C (OC) from fruit extracts of Garcinia yunnanensis Hu. A series of experiments and computational approaches were employed to improve the efficiency of screening for optimal MIP systems in the study. The molar ratio (1: 4) was eventually chosen based on the comparison of the binding energy of the complexes between the template (OC) and the functional monomers using density functional theory (DFT) at the RI-PBE-D3-gCP/def2-TZVP level of theory. The binding characterization and the molecular recognition mechanism of MIPs were further explained using the molecular modeling method along with NMR and IR spectra data. The reusability of this approach was demonstrated in over 20 batch rebinding experiments. A mass of 140.5 mg of OC (>95% purity) was obtained from the 5 g extracts, with 2 g of MIPs with the best binding properties, through a gradient elution program from 35% to 70% methanol-water solution. At the same time, another structural analog, 46.5 mg of guttiferone K (GK) (>88% purity), was also obtained by the gradient elution procedure. Our results showed that the structural analogs could be separated from the crude extracts by the molecularly imprinted solid-phase extraction (MISPE) using a gradient elution procedure for the first time.
Although paraquat is a widely used herbicide, it is toxic to humans if ingested or absorbed through an open wound. To improve the safety of paraquat, a new formulation of paraquat based on photoresponsive polymers was exploited. Photoresponsive β-cyclodextrin polymer microspheres (AZO-CD) were synthesized via a host-guest interaction between β-cyclodextrin and azobenzene. AZO-CD were characterized by Fourier transform infrared spectrometry, circular dichroism, ultraviolet (UV) spectrophotometry, and thermogravimetric analysis, and their photoresponsiveness was also evaluated. AZO-CD were used to load paraquat, which yielded photoresponsive paraquat-loaded microspheres. For the paraquat-loaded microspheres, irradiation with UV light or sunlight induced the isomerization of azobenzene into the cis form. Then, the cis-azobenzene was liberated from the cavities of the β-cyclodextrin. The paraquat-loaded microspheres released paraquat continuously over time. Furthermore, under UV light, the herbicidal capacity of the paraquat-loaded microspheres against barnyard grass was comparable to that of free paraquat at the same dose. Our findings show that loading paraquat into AZO-CD provides a safe and environmentally friendly herbicide formulation.
Nanometer molecularly imprinted polymers (nano‐MIPs) spherical particles with specific recognition of sialic acid (SA) were synthesized by electrochemically mediated atomic transfer radical polymerization (eATRP) combined with the precipitation method. SA was used as template molecules, 4‐vinylphenylboronicacid (4‐VPBA) as functional monomer, and ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent. The successful synthesis of spherical nanometer MIP particles had been verified by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and Malvern particle size instruments. The effects of the potential adjustment on the morphology, size, and particle size distribution of MIP particles were further investigated. By adjusting the potential for polymerization, nanoparticles with average sizes of 160.32nm, 275.87nm, and 331.99nm were obtained. The recognition performance of nano‐MIPs for SA had been characterized by an UV‐Vis spectrophotometer and the satisfactory imprinting factor (IF) was 1.54. This article is protected by copyright. All rights reserved
During the last few years, separation techniques using molecularly imprinted polymers (MIPs) have been developed, making breakthroughs using magnetic properties. Compared to conventional MIPs, magnetic molecularly imprinted polymers (MMIPs) have advantages in sample pretreatment due to their high specificity and selectivity towards analytes as a result of their larger specific surface areas and highly accessible specific binding sites. The techniques of isolation of active compounds from natural products usually require very long process times and low compound yields. When MMIPs are used in sample separation as Solid Phase Extraction (SPE) sorbents, the MMIPs are introduced into the dissolved sample and spread evenly, and they form bonds between the analyte and the MMIPs, which are then separated from the sample matrix using an external magnetic field. This process of separating analytes from the sample matrix makes the separation technique with MMIPs very simple and easy. This review discusses how to synthesize MMIPs, which factors must be considered in their synthesis, and their application in the separation of active compounds from natural products. MMIPs with magnetic core-shells made by co-precipitation can be a good choice for further development due to the high synthesis yield. Further optimization of the factors affecting the size and distribution of magnetic core-shell particles can obtain higher synthesis yields of MMIPs with higher adsorption capacity and selectivity. Thus, they can isolate target compounds from natural plants in high yields and purity.
The sensitive electrochemical sensing platforms were fabricated using molecularly imprinted polymer (MIP) based technique for mycotoxins [Aflatoxin B1 (AFB1) and Fumonisin B1 (FuB1)] detection. Polyaniline was used as a MIP matrix synthesized using the chemical oxidative polymerization method in the presence of AFB1 and FuB1toxins as the template molecules. Fourier transform infrared spectroscopy and electrochemical techniques were used for the characterization of the synthesized MIPs. The proposed biosensors exhibited good sensitivity of 7.037 and 9.092 µA mL ng-1 cm-2 with the lower detection limits of 0.313 and 0.322 pg mL-1 for AFB1 and FuB1. Both sensors showed good linearity amidst the sensing range of 1 pg mL-1 to 500 ng mL-1. The fabricated sensors open up a promising strategy to detect AFB1 and FuB1 as an alternative for biomolecules with enormous specificity, quick responsiveness, and cost-effectiveness. These fabricated sensors manifest good analytical performance compared to other reported MIP based sensors for AFB1 and FuB1 detection.
The Oral route of administration forms the heartwood of the ever-growing tree of drug delivery technology. It is one of the most preferred dosage forms among patients and controlled release community. Despite the high patient compliance, the deliveries of anti-cancerous drugs, vaccines, proteins etc. via the oral route are limited and have recorded a very low bioavailability. The oral administration must overcome the physiological barriers (low solubility, permeation and early degradation) to achieve efficient and sustained delivery. This review aims at highlighting the conventional and modern-age strategies that address some of these physiological barriers. The modern age designs include the 3D printed devices and formulations. The superiority of 3D dosage forms over conventional cargos is summarized with a focus on long-acting designs. The innovations in Pharmaceutical organizations (Lyndra, Assertio and Intec) that have taken giant steps towards commercialization of long-acting vehicles are discussed. The recent advancements made in the arena of oral peptide delivery are also highlighted. The review represents a comprehensive journey from Nano-formulations to micro-fabricated oral implants aiming at specific patient-centric designs.
Responsive molecularly imprinted microgels (MIGs) have gained a lot of interest due to their responsive specificity and selectivity for target compounds. Study on MIGs is rapidly increasing due to their quick responsive behavior in various stimuli like pH and temperature. MIGs show unique property of morphology control on in-situ synthesis of nanoparticles in response of variation in reactant concentration. Literature related to synthesis, parameters, characterization, applications and prospects of MIGs are critically reviewed here. Range of templates, monomers, initiators and crosslinkers are summarized for designing of desired MIGs. This review article describes effect of variation in reactants combination and composition on morphology, imprinting factor and percentage yield of MIGs. Hydrolysis of similar templates using MIGs is also described. Relation between percentage hydrolysis and hydrolysis time of targets at different temperatures and template:monomer ratio is also analyzed. Possible imprinting modes of ionic/non-ionic templates and its series are also generalized on the basis of previous literature. MIGs are investigated as efficient anchoring vehicles for adsorption, catalysis, bio-sensing, drug delivery, inhibition and detection.
The food and environmental samples contaminated with antibiotic residues poses drastic risk to human health. It is believed that the continuous use of destructive chemicals cause numerous health problems including allergic reaction, hypertension, temporary loss of vision, headache, muscles pain, and serious hormonal dysfunction. The presence of antibiotics in food and environmental samples has imposed to look for several facile, cost effective and selective analytical tools to detect them at trace level. Molecular imprinting of polymer (MIP) is an artificial recognition technique for selective and specific detection of template molecule from real samples. MIPs are upcoming robust technique that may help in detection of antibiotics without any pre-treatment of samples. Modern MIPs technique has the sensitivity to detect and quantify the antibiotics residues in food and environmental samples because of their predetermined shape and selectivity, sensitivity, easy handling, low cost and recyclability. The review gives an overview about the classification of antibiotics and excessive use of antibiotics to contaminate food. It gives an overview of the health effect of contaminated food, environmental samples and applications of different approaches of molecular imprinting techniques used for detection and isolation of antibiotics in these samples. It also briefs the different methodology adapted for polymer matrix used in MIP and their efficiencies.
This study presents the development of a cholesterol-selective adsorbent that can be easily produced for the highly efficient removal of cholesterol from milk. A fundamental affinity separation technology which was combined with the specific recognition property of molecular imprinting with a high flow rate and the resulting cryogel was used to separate cholesterol separation from milk samples. The proposed material offers a reasonable pore size and structure, high surface area, and mechanical and chemical stability. To separation the cholesterol from milk, poly(2-hyroxyethyl methacrylate-N-methacryloyl-l-tryptophan methylester) cryogel beads were prepared using a functional monomer that allowed the formation of cholesterol-selective binding sites and enhanced the selective removal of cholesterol from milk. Characterization studies of the cholesterol-imprinted cryogel beads (CHO-MIPs) were carried out by attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy, elemental analysis, water-uptake tests and surface area measurements. The interactions between CHO-MIP and cholesterol were investigated and the factors affecting the adsorption of cholesterol were determined to find optimum conditions. Reusability as a measure of the continuity of the prepared CHO-MIPs was also investigated. The selectivity of the CHO-MIP beads was determined by using competing molecules (estradiol and progesterone), which are cholesterol analogues. The experimental data showed that the specific areas of the CHO-MIP and non-imprinted (NIP) cryogel beads were 17.6 and 14.7 m2/g, respectively. The CHO-MIP cryogel beads were 4.77 and 2.76 fold more selective for cholesterol compared to estradiol and progesterone respectively. The cholesterol adsorption capacity of the CHO-MIP beads was 288.72 mg/g when the cholesterol concentration in solution was 3.0 mg/mL. After eight adsorption-desorption cycles, the adsorption capacity of the CHO-MIP beads decreased by 9.21 %. The Langmuir-Freundlich isotherm model was well fitted as compare to Langmuir and Freundlich isotherms. The obtained kinetics data showed that a pseudo-second order mechanism was predominant for the CHO-MIP cryogel bead adsorption.
Due to the circadian rhythm regulation of almost every biological process in the human body, physiological and biochemical conditions vary considerably over the course of a 24-h period. Thus, optimal drug delivery and therapy should be effectively controlled to achieve the desired therapeutic plasma concentrations and therapeutic drug responses at the required time according to chronopharmacological concepts, rather than continuous maintenance of constant drug concentrations for an extended time period. For many drugs, it is not always necessary to constantly deliver a drug into the human body under disease conditions due to rhythmic variations. Pulsatile drug delivery systems (PDDSs) have been receiving more attention in pharmaceutical development by providing a predetermined lag period, followed by a fast or rate-controlled drug release after application. PDDSs are characterized by a programmed drug release, which may release a drug at repeatable pulses to match the biological and clinical needs of a given disease therapy. This review article focuses on thermoresponsive gating membranes embedded with liquid crystals (LCs) for transdermal drug delivery using PDDS technology. In addition, the principal rationale and the advanced approaches for the use of PDDSs, the marketed products of chronotherapeutic DDSs with pulsatile function designed by various PDDS technologies, pulsatile drug delivery designed with thermoresponsive polymers, challenges and opportunities of transdermal drug delivery, and novel approaches of LC systems for drug delivery are reviewed and discussed. A brief overview of all academic research articles concerning single LC- or binary LC-embedded thermoresponsive membranes with a switchable on-off permeation function through topical application by an external temperature control, which may modulate the dosing interval and administration time according to the therapeutic needs of the human body, is also compiled and presented. In the near future, since thermal-based approaches have become a well-accepted method to enhance transdermal delivery of different water-soluble drugs and macromolecules, a combination of the thermal-assisted approach with thermoresponsive LCs membranes will have the potential to improve PDDS applications but still poses a great challenge.
During the last decade, templating polymers using molecular imprinting has developed into an efficient strategy for the creation of selective synthetic receptor materials based on cross-linked polymeric networks. However, incubation studies and scavenger applications using conventional molecularly imprinted polymers (MIPs) are rather time consuming, as they require centrifugation and extraction steps. An innovative method circumnavigating this problem is the use of magnetic particles facilitating separations via magnetic field. Nowadays, magnetic materials and especially nanoparticles find widespread applications in analytical chemistry, medicine, and biotechnology. Consequently, combining molecularly imprinting materials with magnetic properties provides a new class of smart synthetic receptors, i.e., magnetic molecularly imprinted polymers (MMIPs). This review gives an overview on these multifunctional materials prepared for biomacromolecules such as enzymes, proteins, DNA and viruses including synthesis, applications and also highlights future trends and perspectives in this emerging research field.
Deltamethrin (DM) is one of the most efficient pyrethroid insecticides, which is widely applied to the control of insect pests in tea. In this work, efficient molecularly imprinted polymers (MIPs) were synthesized using DM as the template and acrylamide as the functional monomer, in conjunction with two‐step seed swelling polymerization. Scanning electron microscopy, Fourier transform infrared spectroscopy, and Brunauer–Emmett–Teller surface area analysis confirmed the staggered pore structure and the presence of binding site in DM MIPs. The adsorption properties of the DM MIPs were also investigated based on assessing equilibrium adsorption as well as kinetic modeling and solid‐phase extraction. Isothermal equilibrium adsorption experiments show that the adsorption behavior is consistent with the Freundlich and Halsey models, indicating heterogeneous multilayer specific adsorption. Fitting of the kinetic data demonstrates that chemical adsorption could be the rate‐limiting step in DM extraction, which is consistent with a pseudo‐second‐order kinetic model. Using the imprinted polymers as solid‐phase extraction filler, the DM recoveries from various teas were greater than 80% and exceeded those of the structural analogs cypermethrin, lambda‐cyhalothrin, and bifenthrin. These results confirm that the MIPs exhibit specific adsorption of this analyte. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 136, 47415.
Concepts leading to single enantiomers of chiral molecules are of crucial importance for many applications, including pharmacology and biotechnology. Recently, mesoporous metal phases encoded with chiral information have been developed. We propose here to fine‐tune the enantioaffinity of such structures by imposing an electric potential, which can influence the electrostatic interactions between the chiral metal and the target enantiomer. This allows increasing the binding affinity and thus the discrimination between two enantiomers. The concept is illustrated by generating chiral encoded metals in a microfluidic channel via the reduction of a platinum salt in the presence of a liquid crystal and L‐tryptophan as a chiral model template. After removal of the template molecules, the modified microchannel retains a pronounced chiral character. Its chiral recognition efficiency can be fine‐tuned by applying a suitable potential to the metal phase. This enables the separation of both components of a racemate flowing through the channel. The approach constitutes a promising and complementary strategy in the frame of chiral discrimination technologies.
Concepts leading to single enantiomers of chiral molecules are of crucial importance for many applications, including pharmacology and biotechnology. Recently, mesoporous metal phases encoded with chiral information have been developed. Fine‐tuning of the enantioaffinity of such structures by imposing an electric potential is proposed, which can influence the electrostatic interactions between the chiral metal and the target enantiomer. This allows the binding affinity between the chiral metal and the target enantiomer to be increased, and thus, the discrimination between two enantiomers to be improved. The concept is illustrated by generating chiral encoded metals in a microfluidic channel by reduction of a platinum salt in the presence of a liquid crystal and l‐tryptophan as a chiral model template. After removal of the template molecules, the modified microchannel retains a pronounced chiral character. The chiral recognition efficiency of the microchannel can be fine‐tuned by applying a suitable potential to the metal phase. This enables the separation of both components of a racemate flowing through the channel. The approach constitutes a promising and complementary strategy in the frame of chiral discrimination technologies.
This chapter contains sections titled: Solid‐Phase Microextraction HS‐SPME‐GC Applications Using MOF‐Based Coatings DI‐SPME‐LC Applications Using MIP‐Based Coatings Conclusions and Trends Acknowledgements
There is great interest in the preparation of synthetic receptor-based recognition units for cheap, robust, economic, and selective chemical sensors. Molecular imprinting provides the technology to prepare these synthetic units. There are still more and more syntheses of artificial molecular recognition constructs using analytes or their close structural analogues as templates for molecular imprinting. Stability of complexes of these constructs with the target analytes are often similar to those of biological receptors. Therefore, subsequent polymerization of these complexes results in molecularly imprinted polymers (MIPs) that have a selectivity close to that revealed by natural receptors.
The book summarizes the latest developments and applications of molecular imprinting for selective chemical sensing with each chapter devoted to different analytical applications of molecularly imprinted polymers. Specific chapters include: designing of molecular cavities aided by computational modelling, application of molecularly imprinted polymers for separation as well as sensing of pharmaceuticals and nucleotides.
The book is suitable for academics, postgraduates, and industrial researchers active in analytical chemistry, synthetic organic chemistry, molecular recognition, electrochemistry, and spectroscopy.
In the present study, a new, green, and biodegradable molecularly imprinted polymer (MIP) based on modified cellulose is introduced for the drug furosemide. First, microcrystalline cellulose was converted into cellulose acrylate (CA). Then the prepared CA underwent self-crosslinking in the drug preassembly solution. The preassembly solution of the drug was also prepared using furosemide as the template molecule and acrylamide as the functional monomer in an aqueous medium. The results obtained from the binding and selectivity studies indicate the successful preparation of the CA-based MIP (CA-MIP) in aqueous solution. In the final step, an in vitro release study of furosemide from the synthesized polymers was carried out in a pH = 7.41 phosphate-buffered saline solution at 37 °C. The drug release profiles showed that the release rate of the CA-MIP is more controlled than that of the corresponding nonimprinted polymer, especially at the early stages of release. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45581.
In the present study, a green and biodegradable molecularly imprinted polymer (MIP) based on cellulose is introduced for Furosemide drug for the first time. Firstly, sodium carboxymethyl cellulose (CMC) was synthesized from microcrystalline cellulose. Then the prepared CMC underwent cross-linking in the drug pre-assembly solution using 2-hydroxyethyl methacrylate as the comonomer and ammonium peroxydisulfate as the CMC activating agent. The pre-assembly solution of the drug was also prepared using Furosemide as the template molecule and acrylamide as the functional monomer in aqueous medium. The obtained results from binding and selectivity studies indicated the successful preparation of the CMC-based MIP (CMC-MIP) in aqueous solution. Besides, structural, thermal, and morphological characterization of the prepared system was investigated. In the final step, the In vitro release study of Furosemide from the synthesized polymers was carried out in pH=7.41 phosphate buffered saline solution at 37°C. According to the results, the CMC-MIP had a larger drug loading capacity and a higher amount of drug release at its equilibrium state compared to the corresponding non-imprinted polymer (CMC-NIP). Moreover, the drug release profiles showed that the drug release rate of the CMC-MIP is more controlled than that of the CMC-NIP, especially at the early stages of release.
With the advent of “intelligent” polymeric systems, the use of stimuli-responsive in situ gelling systems has been revolutionized. These interesting polymers exist as free-flowing aqueous solutions before administration and undergo a phase transition to form a viscoelastic gel in a physiological environ through various stimuli such as temperature, pH, solvent, biochemical, magnetic, electric, ultrasound, and photo-polymerization. These smart polymers are endowed with numerous merits such as ease of administration, sustained release, reduced frequent administration with improved patient compliance, and targeted and spatial delivery of a drug with reduced frequency of side effects. Concerted efforts are being made to modify these polymers synthetically because they hold immense potential in various fields such as polymer chemistry, materials science, pharmaceutics, bioengineering medicine, and chemical engineering. In addition to novel drug delivery, these smart polymeric systems have exhibited tremendous applications in tissue engineering, regenerative biomedicine, molecular imprinting, cancer therapy, gene delivery, theranostic and other applications. The current review mainly focuses on the fundamental principles involved during in situ gelling, use of various “smart” drug-delivery formulation systems through diverse routes for their administration, as well as their well-documented biomedical applications. The pertinent literature, marketed formulations, and recent advances on these stimuli-responsive sol-gel-transforming systems are also discussed.
Acute inflammation is a protective response of the body to harmful stimuli, such as pathogens or damaged cells. However, dysregulated inflammation can cause secondary damage and could thus contribute to the pathophysiology of many diseases. Inflammasomes, the macromolecular complexes responsible for caspase-1 activation, have emerged as key regulators of immune and inflammatory responses. Therefore, modulation of inflammasome activity has become an important therapeutic approach. Here we describe the design of a smart nanodevice that takes advantage of the passive targeting of nanoparticles to macrophages and enhances the therapeutic effect of caspase-1 inhibitor VX-765 in vivo. The functional hybrid systems consisted of MCM-41-based nanoparticles loaded with anti-inflammatory drug VX-765 (S2-P) and capped with poly-L-lysine, which acts as a molecular gate. S2-P activity has been evaluated in cellular and in vivo models of inflammation. The results indicated the potential advantage of using nanodevices to treat inflammatory diseases.
Cargo delivery from mesoporous silica nanoparticles loaded with sulforhodamine B and capped with a difluoroboron-dipyrromethene (BODIPY) derivative was triggered by a NO2-induced oxidative process.
A wide range of boronic acid and nitrocatechol end-functionalized homopolymers were prepared via RAFT polymerization from functionalized chain transfer agents (CTAs). Next, the coupling reaction between complementary end-functionalized blocks led to amphiphilic block copolymers (BCPs) featuring a multistimuli-responsive reversible covalent boronate ester junction between both blocks. The efficiency of the coupling reaction, the self-assembly of these BCPs in aqueous medium into nanoaggregates, and their ability to encapsulate hydrophobic molecules were assessed and characterized by NMR (1H, DOSY), fluorescence spectroscopy, DLS, cryo-TEM, and SEC. The multiresponsiveness of the covalent junction was then investigated upon applying various stimuli such as pH change, addition of sugar, and UV light, resulting in the dissassembly of BCP-based nano-objects and the release of the fluorescent probe. Interestingly, the release profile of model molecules was found to be readily and finely modulated through the nature of stimuli and also by successively applying different stimuli.
Molecular imprinted polymers (MIP) are promising and versatile materials that have been used for the determination of many different analytes. In the last few years, MIPs have been substantially employed for various biomedical applications, especially drug delivery systems (DDS), owing to some of their unique features such as specific recognition by imprinting the desired analyte, suitability in rough experimental conditions, and targeted and sustained drug release. Hence, this review is focused on the development of strategies undertaken for their application to drug delivery systems involving several different administration routes (i.e. transdermal, ocular and oral routes) published between 2014 and now. Herein, we have also highlighted the summaries of published works, in order to gain a better understanding of the synthetic strategies employed and the analytical performances of the reported MIPs, in addition to pointing out the challenges and future perspectives of MIP based DDS.
Certain proteins undergo a substantial conformational change in response to a given stimulus. This conformational change can manifest in different manners and result in an actuation, that is, catalytic or signalling event, movement, interaction with other proteins, and so on. In all cases, the sensing-actuation process of proteins is initiated by a recognition event that translates into a mechanical action. Thus, proteins are ideal components for designing new nanomaterials that are intelligent and can perform desired mechanical actions in response to target stimuli. A number of approaches have been undertaken to mimic nature's sensing-actuating process. We now report a new hybrid material that integrates genetically engineered proteins within hydrogels capable of producing a stimulus-responsive action mechanism. The mechanical effect is a result of an induced conformational change and binding affinities of the protein in response to a stimulus. The stimuli-responsive hydrogel exhibits three specific swelling stages in response to various ligands offering additional fine-tuned control over a conventional two-stage swelling hydrogel. The newly prepared material was used in the sensing, and subsequent gating and transport of biomolecules across a polymer network, demonstrating its potential application in microfluidics and miniaturized drug-delivery systems.
Thermo- and pH-sensitive hydrogels were synthesized using N-isopropylacrylamide and Guar gum (GG) and crosslinked with gluteraldehyde (GA). Sinomenine hydrochloride (SH-HCl) was employed as the model drug to investigate the release characteristics of the hydrogels. The lower critical solution temperature (LCST) of the poly(N-isopropylacrylamide)-g-Guar gum (PNIAAm-g-GG) was shown to be approximately 37.5°C, and the release rate of SH-HCl was demonstrated to be faster below the LCST of the polymer than above the LCST. When the temperature was changed across the LCST, reversible and thermoresponsive release behavior was observed. In the presence of pH 6.8 phosphate buffer solution (PBS) or a high salt concentration, the release rate of SH-HCl from the hydrogel was slower than in pH 1.0 HCl. When pH changed across 1.0-6.8, reversible and pH-responsive release behavior was also observed. Various parameters such as hydrogel strength, permeability and viscosity were calculated and the results were discussed in terms of the nature of the polymer.
Molecular imprinting is a technique for creating recognition sites for a specific analyte in a synthetic polymer. The artificially generated recognition sites have their shapes, sizes, and chemical functionality complementary to the analyte, and are capable of rebinding the analyte molecules in preference to other closely related structures. Molecularly imprinted polymers (MIPs) have been used as the stationary phase in chromatography, as artificial antibodies in immunoassays, as recognition elements in sensors, and as enzyme mimics in catalysis. This paper outlines the applications of MIPs as antibody mimics in radioimmunoassays and enzyme-linked sorbent assays. Recent developments in the synthesis and assay of MIPs in aqueous phases is also presented. Progress in microfabrication and molecular imprinting is described with an eye towards the generation of MIP-based miniaturized devices for analytical and diagnostic applications.
In an earlier communication we reported the synthesis of hydrogels containing an imidazole group and the polymer conjugate which formed a charge transfer complex. The catalytic activity of imidazole enhanced the rate of release of p-nitrophenol. To further extend this approach to polymer conjugates which cannot form such complexes, we now show how the functional groups in such cases can be brought in proximity by metal-ion coordination and molecular imprinting techniques. The hydrolysis of the inactive esters from these hydrogels takes place under facile conditions and is pH responsive.
The molecular imprinting technology is becoming a versatile tool in constructing tailor-made molecular recognition elements. However, no oxidoreductase mimics which can be utilized for the amperometric sensor has ever been developed using molecularly imprinting technology. Glycated hemoglobin, HbA1c, is an important indicator for diabetic control. In order to develop a novel diagnostic system for the measurement of HbA1c, we developed molecularly imprinting technology based artificial enzyme which can catalyze the oxidative cleavage of fructosyl valine, a model compound for HbA1c. Based on our previous report, that polyvinylimidazole functioned as the catalyst for this reaction, we developed the molecularly imprinted catalyst (MIC). Molecularly imprinted catalyst was synthesized by imprinting polyvinylimidazole based polymer using fructosyl valine (Fru-val) that is the model compound for HbA1c as template molecules, based on both typical principles for molecular imprinting, noncovalent and covalent approaches. Fructosyl valine bound to the imprinted polymer more than two times higher than the control polymer, which was prepared in the same way but without the template molecule. The MIC-employing sensor showed high current response to Fru-val compared with the sensor employing the control polymer, due to the increase in the affinity toward cis-diol harboring compound. The amperometric sensor employing MIC showed the selectivity toward Fru-val compared with the sensor signal toward fructosyl-ε-lysine (Fru-ε-lys), while the sensor employing the control polymer showed almost identical responses to Fru-val as that to Fru-ε-lys.
Acceleration property of a cross-linked polymer catalyst for the hydrolysis of N-dodecanoyl leucine-p-nitrophenyl ester is attributed to the molecularly imprinting of phenyl-1-undecylcarbonylamino-3-methylbutyl phosphonate as the template of transition-state analogue (TSA) and 4-[(3′-methacryloylamino)ethyl]imidazole as the binding site of the polymer catalyst. Equimolar complex of the template of the TSA and the binding site of imidazole-containing monomer through the electrostatic interaction and hydrophobic effect was confirmed by 1H NMR measurements and the complex was copolymerized with hydrophobic styrene monomer and 10% divinylbenzene cross-linker. A control polymer without the template, but with the cross-linker, was also prepared. After removal of the template, imidazole-containing imprinted polymer gave a ca. two-fold rate-enhancement in comparison to the non-imprinted polymer.
We characterize the structures of various polyelectrolyte block copolymer micelles in dilute aqueous solution as a function of pH and ionic strength. The block copolymers carry a common core block, 2-(diethylamino)ethyl methacrylate (DEAEMA), and one of three coronal blocks, 2-(dimethylamino)ethyl methacrylate (DMAEMA), poly(ethylene oxide) (PEO), and DMAEMA, whose side chain amine groups are selectively quaternized with benzyl chloride (Q-DMAEMA). The PEO−DEAEMA, DMAEMA−DEAEMA, and Q-DMAEMA−DEAEMA copolymers form micelles with electrostatically neutral, weakly charged, and highly charged coronae, respectively. We adjust the fractional charge α on the DEAEMA and DMAEMA blocks by adjusting the solution pH. For DMAEMA−DEAEMA micelles increasing the fractional charge α swells the micelle corona while decreasing the aggregation number due to electrostatic repulsions. The decrease in aggregation number is also observed with increasing α for the PEO−DEAEMA and Q-DMAEMA−DEAEMA micelles, due to electrostatic repulsions between the hydrophobic DEAEMA blocks. Increasing the ionic strength causes the DMAEMA−DEAEMA micelle corona to shrink as the salt screens electrostatic repulsions within the corona. In all three copolymers increases in the ionic strength cause the micelle aggregation number to increase by screening the electrostatic repulsions between chains. Trends in the corona thickness with varying fractional charge and ionic strength are compared with a number of theoretical models providing additional insight into the micelle structure.
A new type of monomer, called Imprinter, combined with its copolymerization with a stimuli-sensitive monomer, allows gels with receptor sites of reversible affinity to be created. Imprinter-Q is a dimeric monomer that has two cationic groups linked by a 1,2-glycol bond, which is easily cleavable. Weakly cross-linked gels have been prepared using Imprinter-Q, N-isopropylacrylamide, and cross-linker N,N‘-methylenebis(acrylamide). After breaking the 1,2-glycol link, the members of each cationic pair are close together, and they can capture target molecules via a multiple-point electrostatic interaction. The higher affinity of these gels for disodium nitroisophthalate (NPA) or dipotassium naftalenedicarboxylate (NDC) in comparison with control gels, which were prepared with randomly distributed cationic groups, proved that the gels prepared with Imprinter-Q memorized the position of the pairs of cationic groups after swelling and reshrinking. Although the efficient adsorption was expected to depend on the correspondence between the spacing of the two juxtaposed cationic groups of the gel and the spacing of the two anionic groups of the adsorbate, it was found that NPA and NDC (carboxyl spacing 60% longer than in NPA) are adsorbed with similar efficiency. The control gels experienced difficulty in forming pairs, and their affinity for NPA or NDC decreased exponentially as a function of cross-linker concentration. In contrast, the topological constrains were completely absent in the imprinted gels, showing that memorization had been achieved. This “conformational imprinting effect” was tested for several concentrations of Imprinter-Q and permanent cross-linkers.
With the aim of developing polymeric gels sensitive to external stimuli and able to reversibly adsorb and release divalent ions, we prepared copolymer gels of N-isopropylacrylamide (NIPA) and N,N‘-cystaminebis(acrylamide) (BAC) weakly cross-linked with N,N‘-methylenebis(acrylamide) (BIS). After polymerization, the −S−S− bonds of BAC mers were broken and oxidized to form pairs of sulfonic groups. The juxtaposition of two anionic groups favors the interaction with a divalent cation. Calcium adsorption experiments showed that the gels prepared in this way memorized the position of the pairs of sulfonic groups after swelling and reshrinking. This “imprinting” effect was tested for several concentrations of adsorbing groups and permanent cross-linkers. The control gels prepared with 2-acrylamido-2-methylpropanesulfonic acid (AMPS), where sulfonic groups were randomly distributed, showed difficulty in forming pairs. Their affinity for calcium ions decayed exponentially as a function of cross-linker concentration. In contrast, the affinity of the imprinted gels was much greater than that of random gels and did not decrease with BIS, showing that memorization has been achieved.
The synthesis of a confined class of chiral organic catalysts via a bulk imprinting of silica was analyzed. The silica framework was rendered inert via capping of interior surface silanols with trimethylsilyl functionality, which removes framework acidity. The performance of the bulk imprinted catalyst was compared to a Selecto mesoporous silica-grafted catalyst, which have been previously characterized using nitrogen physiosorption. The catalytic activity results show the accessibility and activity of the bulk imprinted sites, with no enantioselectivity.
Selective, stable, molecularly imprinted polymer membranes having intrinsic photoresponsive properties were synthesized. The membranes selectively adsorbed dansylamide from solution. UV irradiation caused desorption of previously adsorbed dansylamide and visible light irradiation led to its re-adsorption.
2-Hydroxy-ethyl-methacrylate-based molecularly imprinted polymer imprinted for hydrocortisone was found to absorb a considerable amount of testosterone. The release of testosterone to water was found to be very slow. Its release was, however, rapid in the presence of the print molecule (hydrocortisone). This opens up the possibility of developing drug release systems capable of modulating the release with respect to the presence of specific molecules. Such systems could be used in the release of steroids and peptides. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1819–1821, 1999
A tailor-made catalytically active polymer catalyzing the bimolecular Diels-Alder reaction is described. Kinetic studies carried out in acetonitrile at 82°C show a 270-fold rate acceleration (kcat/kuncat) for the Diels-Alder reaction between tetrachlorothiophene dioxide and maleic anhydride. The imprinted polymer induces Michaelis-Menten kinetics, with an apparent Km of 42.5 mM and an apparent kcat of 3.82 × 10−2 min−1, respectively. Substrate selectivity, accessible binding site analysis, dissociation constant determination, and inhibition study were also performed.
Poly(methacrylic acid–ethylene glycol dimethacrylate) was prepared using 2-aminopyridine as the imprinting molecule. This molecularly imprinted polymer (MIP) was ground and packed into a micro-column for selective solid phase extraction (SPE) of 2-aminopyridine from 20 μl of sample solution. Non-specific adsorption was also confirmed for a structural analogue. Interestingly one of the isomers, 4-aminopyridine, bound most strongly to the MIP. The implication of resonance and basicity of this isomer molecule can be used to explain its strong binding with the self-assembled functional methacrylic acid (MAA) monomer. The monomer template complexion process was evaluated by Scatchard plots to determine a binding constant. The binding constant value is important for predicting the selectivity of a new MIP. After optimization of the molecular recognition process, a molecularly imprinted solid phase extraction–differential pulsed elution (MISPE–DPE) method was developed for the selective determination of 4-aminopyridine in serum with an analysis time of less than 3 min using a 2-aminopyridine micro-column for surrogate binding. The concentration detection limit was 0.5 μg/ml, which corresponded to an absolute detection limit of 10 ng. A larger sample volume of 845 μl afforded a better concentration detection limit of 52 ng/ml.
A polymeric mimic of chymotrypsin is synthesized by grafting Co(II)-coordinated monomers–template assembly of N-methacryloyl-l-serine, N-methacryloyl-l-aspartic acid, N-methacryloyl-l-histidine and the template N-nicotinoyltyrosylbenzyl ester on crosslinked support poly(glycidylmethacrylate-co-ethylene glycol dimethacrylate). The polymeric mimic obtained after leaching out Co(II), template and ungrafted monomers was found to be hydrolytically active against substrate N-benzyloxycarbonyl-tyrosyl-para-nitrophenyl ester. The cooperative effect amongst functional groups is demonstrated by comparing the hydrolytic activity of the mimic with other polymers comprising only imidazole groups or hydroxyl and imidazole groups. Observed kinetics for hydrolysis of substrate N-benzyloxycarbonyl-tyrosyl-para-nitrophenyl ester obeyed Michaelis–Menten kinetics. The effect of molecular imprinting of the template molecule in enhancing the substrate specificity of the mimic was demonstrated. The mimic synthesized in the absence of Co(II) was found to be hydrolytically inactive.
Synthetic polymer receptors for the online monitoring of bioanalytes are formed directly onto quartz crystal microbalances using surface imprinting techniques. The molded materials are capable of enriching whole cells, viruses and enzymes on the sensor layer surface. Enzyme imprinted polymer layers are also effective as nucleation site for the induction of protein crystallization. Differential measurements are done with a single piezocrystal having two screen-printed gold electrodes for a sensitive and a reference channel.
The macrocyclic bisphosphonate 2 forms complexes with amino alcohols, amines, and amino acid esters with high association constants in polar organic solvents. Exertion of solvophobic interactions inside the macrocyclic cavity in DMSO and methanol leads to specificity for guest molecules with hydrophobic moieties. Experimental evidence is presented for the insertion of the guest molecules' nonpolar groups into the macrocycle's hydrophobic cavity. NMR spectra of complexes with 2 in DMSO show a molecular imprint of the guest molecule; this gives information about its location inside the macrocycle. In aqueous solutions strong self-association of 2 occurs, which is explained by distinct structural similarities between 2 and micelle-forming phospholipids.
Methacrylic acid (MAA) and 2-(trifluoromethyl)acrylic acid (TFMAA) were used to prepare molecularly imprinted polymers exhibiting diastereoselectivity for cinchona alkaloids. Fluorescent spectra of the cinchona alkaloid exhibit a characteristic shift through binding to these polymer particles, originating most likely from the highly acidic residues in the imprinted polymers acting as a proton donator. Our results show that TFMAA based imprinted polymers can be used as polymer reagents for quantitating the cinchona alkaloid bound to the polymers without bound/free separation.
Hydrogels have been used primarily in the pharmaceutical field as carriers for delivery of various drugs, peptides and proteins. These systems have included stimuli-responsive gels that exhibit reversible swelling behavior and hence can show modulated release in response to external stimuli such as pH, temperature, ionic strength, electric field, or specific analyte concentration gradients. The focus of this article is to review molecular imprinting within hydrogels and discuss recent efforts on analyte-responsive intelligent gels, specifically suggesting the possibility of utilizing molecular imprinting strategies to impart analyte specificity and responsiveness within these systems. Molecular imprinting is an emerging field that produces precise chemical architecture that can bind analytes and differentiate between similar molecules with enantiomeric resolution. On the forefront of imprinting gel systems are intelligent, stimuli-sensitive imprinted gels that modify their swelling behavior and in turn modulate their analyte binding abilities. We discuss the challenges creating an imprinting effect in hydrogels and the possibilities of using molecularly imprinted mechanisms within controlled release gels.
Solid phase extraction (SPE) based on molecularly imprinted polymers (MIPs) is a novel approach for sample preparation and preconcentration, gaining increased interest in the fields of environmental, clinical, and food analysis. The first application combining MIPs with SPE for advanced beverage analysis is reported. MIPs for the flavonoid quercetin have been generated, using quercetin as a template molecule in a self-assembly approach and yielding imprinting of 1% of the used template. The MIP achieved a capacity of 0.4 g quercetin per gram polymer and a recovery rate of 98.2%. The application of these synthetic receptors as SPE material for the selective extraction and preconcentration of quercetin from synthetic and red wine samples was investigated. Red wine samples from a French Merlot were directly applied onto the SPE cartridge. The collected fractions were analyzed by high-pressure liquid chromatography. For verification of the obtained results, a similarly prepared nonimprinted polymer and a classical octadecyl silane reversed-phase cartridge were applied as the SPE matrix during control experiments. The MIP enabled the selective extraction of quercetin from a complex matrix, such as red wine, spiked with 8.8 mg per liter quercetin, demonstrating the potential of molecularly imprinted solid phase extraction for rapid, selective, and cost-effective sample pretreatment.
In this work, the stereoselective release behaviors of "low"-swelling molecularly imprinted polymer (MIP) bead matrices in pressed-coat tablet type were studied. Either R-propranolol selective MIP or S-propranolol selective MIP was combined with excipients and racemic propranolol and fabricated into the matrix. Subsequently, the release of different propranolol enantiomers from the matrices was examined. Also, the microscopic structure of the hydrated "low"-swelling MIP matrix was determined using a cryogenic scanning electron microscope in order to compare with that of the hydrated "high"-swelling MIP matrix. In vitro release profiles of the "low"-swelling matrices showed a difference in the release of enantiomers, in that the non-template isomer was released faster than the template isomer. However, in the last phase of dissolution this difference reduced and later reversed, resulting at last in the type of specificity being similar to that obtained previously with "high"-swelling MIP matrices. In summary, MIP beads can be fashioned into matrices and incorporated into different formulations to regulate the resultant stereoselectivity. From the behaviors of stereoselective release observed in MIP matrices, we can conclude that the enantioselective-controlled delivery mechanism of MIPs via formulations depends on the relative affinity of the enantiomer for the template sites, as well as the nature of the polymer, such as hydrophobicity and swellability.
[reaction: see text] A new method is presented for the measurement of enantiomeric excess (ee) utilizing molecularly imprinted polymers (MIPs). The method is demonstrated to be accurate and rapid, as the ee values can be calculated from straightforward concentration measurements. The MIP-based assay can also be adapted to measure the ee of samples of differing initial concentrations.
Separation of ephedrine stereoisomers by molecularly imprinted polymers was performed to study the factors that affect the selectivity and column efficiency. The polymer synthesized with pentaerythritol triacrylate as the cross-linker and chloroform as the porogen was found to have the best overall separation performance. Investigation of the recognition mechanism by NMR and chromatographic analysis revealed that the major binding forces between the polymer stationary phase and ephedrine are the ionic and hydrogen bonding interactions. Studies of the influence of mobile phase compositions on the HPLC analysis have shown that a methanol-aqueous buffer was the suitable mobile phase for the separation in which pH, ionic strength and water content can be adjusted to optimize the chromatographic analysis.
Recent progress in enantiomeric separations by capillary electrochromatography (CEC) is reviewed. The development of simple and robust CEC column technologies plays an important role for popularization of CEC. During the last several years, various approaches for the preparation of enantioselective columns have been reported. Currently, the monolithic column technology (continuous beds) represents the most advanced approach for the preparation of CEC columns. The development of new chiral stationary phase used for CEC is another important issue in this field. Fundamental investigations on electrochromatographic behaviors of various CSPs are necessary in order to understand the separation mechanism and thus improve the separation performance. Some chiral stationary phases performed better under nonaqueous CEC conditions than reversed-phase conditions. Coupling CEC with mass spectrometry (MS) provides a powerful tool for enantiomeric separation. Finally, some applications of enantiomeric separation by CEC are summarized.
Molecular imprinting technology has an enormous potential for creating satisfactory drug dosage forms. Although its application in this field is just at an incipient stage, the use of MIPs in the design of new drug delivery systems (DDS) and devices useful in closely related fields, such as diagnostic sensors, is receiving increasing attention. Examples of MIP-based DDS can be found for the three main approaches developed to control the moment at which delivery should begin and/or the drug release rate, i.e. rate-programmed, activation-modulated, or feedback-regulated drug delivery. The utility of these systems for administering drugs by different routes (e.g. oral, ocular or transdermal) or trapping undesired substances under in vivo conditions is discussed. This review seeks to highlight the more remarkable advantages of the imprinting technique in the development of new efficient DDS as well as pointing out some possibilities to adapt the synthesis procedures to create systems compatible with both the relative instable drug molecules, especially of peptide nature, and the sensitive physiological tissues with which MIP-based DDS would enter into contact when administered. The prospects for future development are also analysed.
Three molecularly imprinted monolithic columns with different length but almost identical column volume had been prepared. It was observed that the separation factors of diastereomers and enantiomers were almost unaffected by column length. However, the short column with dimension of 38 mm x 8 mm i.d. showed much lower resistance to flow rate so that it could be operated at much higher flow rates. By combining stepwise gradient elution with elevated flow rate, the diastereomers of cinchonine and cinchonidine and the enantiomers of Cbz-DL-Trp and Fmoc-DL-Trp were successfully separated within 3 min on the short column with dimension of 38 mm x 8 mm i.d. Based on the above results, a cinchonine imprinted monolithic disk with dimension of 10mm x 16 mm i.d. was further developed. The SEM image and the pore size distribution profile showed that large flow-through pores are present on the prepared monolith, which allowed mobile phase to flow through the disk with very low resistance. Chromatographic performances on the monolithic disk were almost unchanged compared with the long columns. A rapid separation of cinchonine and cinchonidine was achieved in 2.5 min at the flow rate of 9.0 ml/min. Furthermore, it was observed that there was almost no effect of the flow rate on the dynamic binding capacity at high flow rates. In addition, the effect of the loading concentration of analytes on the dynamic binding capacity, namely adsorption isotherm, was also investigated. A non-linear adsorption isotherm of cinchonine was observed on the molecularly imprinted monolith with cinchonine as template, which might be a main reason to result in the peak tailing of template molecule.
Weakly cross‐linked temperature sensitive gels that memorize 4‐aminopyridine molecules were designed and synthesized. The polymer gels show special selectivity, good thermo‐sensitivity and reusability, which would have an enormous potential of application in drug controlled release systems.
Adsorption of Apy by the imprinted and non‐imprinted gels in the shrunken state at 60 °C.
image Adsorption of Apy by the imprinted and non‐imprinted gels in the shrunken state at 60 °C.
A general molecular imprinting approach is proposed to synthesize artificial enzymes to mimic the family of cyclic amide amidohydrolases which share similar active site and catalytic mechanism. The artificial enzymes were constructed by co-polymerizing 4(5)-vinylimidazole-Co2+-methacrylic acid clusters with divinylbenzene micro-spheres in the presence of corresponding substrates. The artificial enzymes mimicked creatininase and hydantoinase by showing specific affinity towards the corresponding substrates in buffer. The artificial hydantoinase also showed specific affinity towards corresponding substrate in organic solvent, and catalyzed the hydrolysis of hydantoin.
An artificial plastic receptor that can discriminate axial asymmetry of optically active binaphthyldiamine derivatives was prepared by the 'molecular imprinting' technique. A light-radical polymerization in the presence of an axially asymmetric compound, (R)-2,2'-bis-methylcarbonylamino-1,1'-binaphthyl (binaphthyldiamine bis-acetamide (BINADA-ac)) as a template molecule with methacrylic acid (MA) as a functional monomer, and ethyleneglycol dimethacrylate (EGDMA) as a crosslinker, at 4 degrees C. The obtained polymer exhibited a superior enantioselectivity to the (R)-enantiomer by HPLC analyses. This plastic receptor should recognize the template molecule with its shape and character of its functional groups. It should be useful in the development of chiral stationary phases for the optical resolutions of axially asymmetric compounds.
Molecularly imprinted polymers (MIPs) known as plastic antibodies (PAs) represent a new class of materials possessing high selectivity and affinity for the target molecule. Since their discovery, PAs have attracted considerable interest from bio- and chemical laboratories to pharmaceutical institutes. PAs are becoming an important class of synthetic materials mimicking molecular recognition by natural receptors. In addition, they have been utilized as catalysts, sorbents for solid-phase extraction, stationary phase for liquid chromatography and mimics of enzymes. In this paper, first time we report the preparation and characterization of a PA for the recognition of blistering chemical warfare agent sulphur mustard (SM). The SM imprinted PA exhibited more surface area when compared to the control non-imprinted polymer (NIP). In addition, SEM image showed an ordered nano-pattern for the PA of SM that is entirely different from the image of NIP. The imprinting also enhanced SM rebinding ability to the PA when compared to the NIP with an imprinting efficiency (alpha) of 1.3.