Article

Albumin nanocarriers for pulmonary drug delivery: An attractive approach

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Abstract

Biodegradable polymers are drawing a great deal of attention in the field of nanotechnology. Albumin, abundantly present in human body, is a biocompatible and biodegradable polymer used in drug delivery systems. It is relatively an inexpensive polymer with several advantages like non-toxicity, high drug loading capacity, binding efficiency with many drugs which qualifies it as an ideal nanocarrier. The present review discusses potential of albumin nanocarriers for pulmonary application. It also discusses feasibility of employing albumin from different sources. Formulation aspects of albumin nanosystems, methods of preparation and dosage form designing are also covered. An array of excipient options suitable to be used in albumin nanocarrier system is presented. Toxicity aspects and applications of albumin nanoparticles with focus on pulmonary application are highlighted. Application of nanoparticulate structures based on albumin in delivery of drugs from category of anticancer agents, vaccines, hormones, anti-asthamatics and anti-inflammatory agents to lungs is covered. This review offers a framework for pharmaceutical scientists in designing of albumin nanoparticles for various pulmonary and systemic applications via inhalation delivery.

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... Albumin is a natural, water-soluble globular protein and attractive macromolecular carrier which has a biodegradable property. Albumin is non-immunogenic, non-toxic, non-antigenic and biocompatible [88,89]. A large number of drugs can be incorporated into the nanoparticle-matrix because albumin molecules have different binding sites [90]. ...
... Albumin structure is shown in Figure 6. Nanomaterials 2020, 10, x FOR PEER REVIEW 11 of 21 demonstrates the successful use of albumin and albumin nanoparticles for cancer treatment [89]. The presence of primary amino acid groups in albumin, such as lysine, indicates a vital role in crosslinking [91]. ...
... The successful use of albumin and an albumin nanoparticle (Abraxane) for cancer treatment [89]. Copyright ©2020, Elsevier. ...
Article
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Biodegradable natural polymers have been investigated extensively as the best choice for encapsulation and delivery of drugs. The research has attracted remarkable attention in the pharmaceutical industry. The shortcomings of conventional dosage systems, along with modified and targeted drug delivery methods, are addressed by using polymers with improved bioavailability, biocompatibility, and lower toxicity. Therefore, nanomedicines are now considered to be an innovative type of medication. This review critically examines the use of natural biodegradable polymers and their drug delivery systems for local or targeted and controlled/sustained drug release against fatal diseases.
... Albumin is a natural, water-soluble protein and an attractive macromolecular carrier that is biodegradable. Albumin is non-immunogenic, non-toxic and biocompatible [31,32]. A large number of drugs can be included in the matrix of nanoparticles, since albumin molecules have different binding options [33], and are successfully used to treat cancer [32]. ...
... Albumin is non-immunogenic, non-toxic and biocompatible [31,32]. A large number of drugs can be included in the matrix of nanoparticles, since albumin molecules have different binding options [33], and are successfully used to treat cancer [32]. Commercially available forms of albumin are ovalbumin (egg white), human serum albumin, albumin extracted from soybeans, albumin present in bovine serum capsules, grain and milk albumin [34]. ...
... Hydroxyapatite is widely used in biomedicine and is considered the best option in the pharmaceutical field due to its superior bioactivity and biocompatibility [35]. Hydroxyapatite is obtained from mineral compounds of human bones, teeth and hard tissues [32]. ...
Article
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This paper provides an overview of the current state of research in the field of the use of biodegradable polymers for medical purposes. The relevance of the research topic is noted, current trends in the development of biodegradable polymers, the creation of polymer protective coatings, polymers with shape memory effect for medical devices for various applications are described. The classification of modern biodegradable polymers, features of synthetic and natural biopolymers is presented, their advantages and disadvantages are indicated. Biodegradable polymers for drug encapsulation and delivery, the possibility of creating nanostructured polymers for pharmaceuticals are presented. The prospects for the future development of the use of biodegradable polymers in medicine are analyzed and described.
... [15][16][17][18][19][20][21] An additional class of biological-originated polymers for hydrogels are those having proteins as building blocks, such as collagen, soy proteins, fibroin (silk), keratin and specifically to this work, also bovine serum albumin (BSA), all of which have been used for making hydrogels. [22][23][24][25][26][27] The appearance of the so-called 'smart' hydrogels, has greatly expanded the range of available capacities for delivering molecules. 28,29 However, they usually require additional chemical modification on the polymer backbone that are not widely available, and they can be expensive, all in which might hamper their application. ...
Article
Hydrogels are common platforms for drug delivery applications. Amongst the different loading and release methodologies, physisorption loading and passive release stand out for their straightforwardness. However, evaluating the inner environment and the surface of the polymer can be complicated, as they can be much different from the properties of the monomer comprising the hydrogel. Here, we explore the inner environment of macroscopic bovine serum albumin (BSA) hydrogels, by using both the native Trp residues of the protein and the pyranine photoacid as fluorescent probes. Time-resolved fluorescence is used to follow the fast solvation dynamics of Trp and the excited-state proton dissociation of pyranine. The results show that upon gelation, the surface of the BSA within the hydrogel is less accessible to water, i.e., more hydrophobic, as compared to before gelation. This understanding is used to rationalize the different drug binding efficiencies of the anti-cancer drug doxorubicin to the hydrogel at different pH values, which changes the charge of the molecule. Finally, we give proof for the hydrogels capacity to effectively function as drug-carrier systems in vitro, using different cancer cell lines over a 7-day period. Our study shows that relatively simple spectroscopic measurements can result in a fundamental structural and chemical understanding of (protein) hydrogels. From an application point of view, our protein hydrogels are very easy to form, without any need of complex chemical modification, they are very low cost as compared to other hydrogels, and show slow and sustained drug release profiles, all very sought-after properties.
... There are some ways for preparation of albumin based nanoparticles such as: coacervation, emulsification, etc. methods [28]. For the biomedical applications a facile aqueous synthesis under ambient conditions are required. ...
Article
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In this study, biotin functionalized bovine serum albumin (BSA-biotin) loaded with curcumin (CUR), was synthesized and evaluated as drug carrier. The aim of this study is evaluation of the curcumin induced apoptosis related proteins, Bcl-2 and Bax expression via targeted albumin based nanoparticles. The synthesized BSA-biotin-CUR was characterized by different techniques such as: TEM, UV–Vis, FTIR, and DLS. The loading efficiency of CUR was 7.9%. The result indicates that the particles were measured around 185.4 nm with a zeta potential of -16.8 mV. Cytotoxicity results on mouse mammary tumor cell line (4T1) confirmed that formulated CUR, BSA-biotin-CUR, has high anticancer effect compared to free CUR. Also, real-time PCR method revealed that BSA-biotin-CUR increased Bax protein expression, and also downregulated Bcl-2 protein in 4T1 cells, which proven the ability of synthesized nanoparticles. We suggest that BSA-biotin-CUR can improve therapeutic effect, of CUR so that it can overcome the limitations of CUR with a great potential for further evaluations and applications.
... Nab technology overlaps with some aspects of the emulsification procedure, as it can be thought of as a contemporary emulsification approach, with the difference that the Nab technology does not require external crosslinking to ensure stability, the use of surfactants is not necessary, and there are more degrees of control within the process. [67] Potential drawbacks of this technique include limitations on the stabilizing agents if they do not naturally contain or cannot be chemically modified to have sulfhydryl and/or disulfide groups. However, it cannot be overlooked that this method has enjoyed broad translational successes. ...
Article
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Protein nanoparticles, PNPs, have played a long‐standing role in food and industrial applications. More recently, their potential in nanomedicine has been more widely pursued. This review summarizes recent trends related to the preparation, application, and chemical construction of nanoparticles that use proteins as major building blocks. A particular focus has been given to emerging trends related to applications in nanomedicine, an area of research where PNPs are poised for major breakthroughs as drug delivery carriers, particle‐based therapeutics or for non‐viral gene therapy.
... Surface modification and material engineering are indispensable steps in biomedical applications. FDA-approved albumin is one of the most abundant and smallest globular proteins in blood plasma, offering many active binding sites for drug loading and modification, high stability, water solubility, biocompatibility, biodegradability, nonimmunogenicity, and nontoxicity [16]. It is, therefore, a good candidate for use as a drug carrier and as a coating agent. ...
Article
Aim: To prepare a novel hybrid system for the controlled release and delivery of curcumin (CUR). Methods: A method for the ultrasound-assisted fabrication of protein-modified nanosized graphene oxide-like carbon-based nanoparticles (CBNPs) was developed. After being modified with bovine serum albumin (BSA), CUR was loaded onto the synthesized hybrid (labeled CBNPs@BSA–CUR). The structure and properties of the synthesized nanoparticles were elucidated using transmission electron microscopy (TEM), atomic force microscopy (AFM), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and x-ray photoelectron spectroscopy (XPS) methods. Results: CBNPs@BSA–CUR showed pH sensitivity and were calculated as controlled CUR release behavior. The drug-free system exhibited good biocompatibility and was nontoxic. However, CBNPs@BSA–CUR showed acceptable antiproliferative ability against MCF-7 breast cancer cells. Conclusion: CBNPs@BSA–CUR could be considered a highly promising nontoxic nanocarrier for the delivery of CUR with good biosafety.
... In this study, human serum albumin was used to make nanoparticles. Albumin, as a polymer that is abundant in the human body, has favorable properties such as biodegradability, biocompatibility, non-toxicity, low cost and high ability to bind to a variety of drugs [28]. In this study, HSA was used to make nanoparticles. ...
Article
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Introduction Microbial resistance is increasing worldwide. Investigations are underway to use nanoparticles as antimicrobial agents to reduce microbial resistance. Materials and methods Seven human pathogenic bacteria were selected according to common hospital infection bacteria: both gram-positive and negative. In this study, imipenem and ciprofloxacin antibiotics were used separately and in combination with human serum albumin and coacervation method for the preparation of nanoparticles. Dynamic light scattering (DLS), scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FT-IR) were used to investigate the properties of nanoparticles. Antibacterial activity was determined and compared using the disk diffusion technique and minimum inhibitory concentration (MIC) was determined. Results The results of DLS for imipenem, ciprofloxacin and the combination of both antibiotics were 85 nm, 135 nm, and 120 nm, and for SEM were 79.9 nm, 122.2 nm, and 111 nm, respectively. All of the synthesized nanoparticles have a spherical shape. The antibacterial effect on the disk diffusion test for Acinetobacter baumannii bacteria was more noticeable in all three HSA nanoparticle compositions than other bacteria. The use of antibiotics in the form of HSA nanoparticles reduced the MIC. This value was more significant for nanoparticles carrying both ciprofloxacin and imipenem on methicillin-resistant Staphylococcus aureus and Streptococcus mutans bacteria. Conclusion From the results of this study, it can be concluded that the use of HSA nanoparticles carrying the aforementioned antibiotics has more antibacterial effect against the bacteria of this study, especially S. mutans, than their free form.
... Polysaccharide-based carriers are abundant and have characteristics that make them elite molecules for delivery (Barclay et al., 2019) when compared with other types of carriers, such as lipid-based systems (Ngan & Asmawi, 2018), synthetic polymers (Emami et al., 2019), proteins (Joshi et al., 2020), and inorganic systems (Cai et al., 2020;Luther et al., 2020). ...
Article
Polysaccharides can be elite carriers for therapeutic molecules due to their versatility and low probability to trigger toxicity and immunogenic responses. Local and systemic therapies can be achieved through particle pulmonary delivery, a promising non-invasive alternative. Successful pulmonary delivery requires particles with appropriate flowability to reach alveoli and avoid premature clearance mechanisms. Polysaccharides can form micro-, nano-in-micro-, and large porous particles, aerogels, and hydrogels. Herein, the characteristics of polysaccharides used in drug formulations for pulmonary delivery are reviewed, providing insights into structure-function relationships. Charged polysaccharides can confer mucoadhesion, whereas the ability for specific sugar recognition may confer targeting capacity for alveolar macrophages. The method of particle preparation must be chosen considering the properties of the components and the delivery device to be utilized. The fate of polysaccharide-based carriers is dependent on enzyme-triggered hydrolytic and oxidative mechanisms, allowing their complete degradation and elimination through urine or reutilization of released monosaccharides.
... Abraxane is a commercially available albumin nanoparticle bound paclitaxel formulation that is used to treat breast cancer . Though encapsulation of a wide range of drugs into albumin nanoparticles has been extensively reported in the literature (Esim & Hascicek, 2021;Joshi et al., 2020;Karami et al., 2020), quantitative aspects of interactions between drugs and nanoparticles have not been addressed well. A wide range of nanoparticles with different physicochemical properties has been known to influence the function and stability of proteins (Dobrovolskaia et al., 2009;Mahmoudi et al., 2011;Piella et al., 2017;Wigginton et al., 2010). ...
Article
Protein-based nanoparticles offer a suitable targeted delivery platform to drugs in terms of biocompatibility, biodegradability and abundance in nature. Physicochemical understanding of drug encapsulation by protein nanoparticles and their impact on protein aggregation is essential. In this work, we have examined quantitative aspects of encapsulation of non-steroidal anti-inflammatory drugs naproxen and diclofenac sodium, and anti-thyroid drug methimazole in nanoparticles of human serum albumin (HSA NPs) by using ultrasensitive calorimetry. Thermodynamic signatures accompanying the interactions revealed that the partitioning of all these drugs in HSA NPs is primarily driven via contributions from desolvation of highly hydrated nanoparticles surface. Furthermore, the effect of these nanoparticles on fibrillation of HSA has also been studied. HSA NPs are determined to be ineffective towards inhibition of fibrillation under employed conditions. However, the extent of inhibition by HSA NPs varies depending upon the structural characteristics of the drugs. Such studies help to gain mechanistic aspects on drug loading into protein-based nanoparticles and are expected to provide useful insights into improving existing nano-drug carriers and their efficiency in preventing protein fibrillation. Communicated by Ramaswamy H. Sarma
... Bovine serum albumin (BSA) is a water-soluble protein with a molecular weight of 66 kDa. It may increase the interaction of drug delivery systems with cells [13] . The outer surfaces of nanoparticular systems can be coated with BSA to ensure a long period of the systemic circulation [14] . ...
Article
The aim of our study was to discover an alternative active substance to tyrosine kinase inhibitors such as erlotinib (Erlo) used in lung cancer treatment and to develop an appropriate and efficient formulation for oral administration of the substance. Newly synthesized zinc (II) phthalocyanine bearing ferrocene groups (Pc-Zn) was chosen as a model drug due to its use in photodynamic therapy. Pc-Zn increased the amount of nicked form (Form II) by 22.90% and decreased the amount of supercoiled form (Form I) by 77.10% in DNA cleavage studies using plasmid pBR322 DNA in the presence of light and oxygen. Liposome formulations containing Pc-Zn (Pc-Zn Lip) or Erlo (Erlo Lip) had small particle size as 450.5±32.4 nm and 187.2±1.6 nm, respectively and coating with bovine serum albumin (BSA) had not significantly changed particle sizes. Pc-Zn loaded liposomes had significantly (p <0.001) cytotoxic effect under light irradiation than Erlo loaded liposomes. Coating with BSA had no significant effect on the cytotoxicity of the formulations. As a result, it was observed that Pc-Zn was more cytotoxic in the presence of light irradiation than Erlo. However, there was no significant difference in cytotoxic effects between the BSA-coated and non-coated Pc-Zn/Erlo formulations.
... To fill these knowledge gaps, further research is necessary to assess the safety of both target and non-target species, while ensuring that animals are managed properly to guarantee the maximum vaccine efficacy. To overcome the disadvantages of conventional drug delivery systems, a lot of research now aims at the development and use of novel delivery platforms, including those operating at the nanoscale [84]. Pharmaceutical-loaded pbENPs can be delivered by aerosolization as a liquid suspension or a dry powder that dissolves after contacting the aqueous environment of the lung epithelium [85]. ...
Article
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The field of veterinary medicine needs new solutions to address the current challenges of antibiotic resistance and the need for increased animal production. In response, a multitude of delivery systems have been developed in the last 20 years in the form of engineered nanoparticles (ENPs), a subclass of which are polymeric, biodegradable ENPs, that are biocompatible and biodegradable (pbENPs). These platforms have been developed to deliver cargo, such as antibiotics, vaccines, and hormones, and in general, have been shown to be beneficial in many regards, particularly when comparing the efficacy of the delivered drugs to that of the conventional drug applications. However, the fate of pbENPs developed for veterinary applications is poorly understood. pbENPs undergo biotransformation as they are transferred from one ecosystem to another, and these transformations greatly affect their impact on health and the environment. This review addresses nanoparticle fate and impact on animals, the environment, and humans from a One Health perspective.
... The global market of anticancer nanoproducts was valued to be about $47.3 billion in 2017 and it is expected to reach $84.4 billion by 2022 with growing CAGR at 12.3% [188]. Many of these commercialised nanoparticulate drug delivery systems enabled better targeting, new modes of action, Table 2 Some commercialised nanoparticulate drug delivery systems [91,126,[189][190][191][192][193][194]. and enhancement of bioavailability of the existing medicinal substances. ...
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The advancement in medical sciences and perturbing limitations of some conventional drug delivery systems has triggered extensive research in nanomedicine, and there have been profound exploitations that promise to revolutionise drug delivery systems. To develop more effective and safer therapeutic medicines, researchers have designed various advanced and multifunctional nanocarrier systems that can provide targeted, sustained, and controlled delivery of drugs. These novel systems are leading to the enhancement of drugs’ systemic circulation, improvement of the pharmacokinetic profile of drugs, and reduction of adverse effect incidences of drugs. Some of the nanoparticulate drug delivery systems that have demonstrated substantial benefits such as polymeric, lipids and metals nanoparticles; liposomes; nanoemulsions; and micelles have already made it to the market. These nanocarriers have greatly influenced the pattern of modern drug therapy to address emerging needs. However, there are some concerns related to toxicological aspects associated with some of these nanocarriers that need to be resolved. This review article was aimed to provide insightful advancements on the applications of nanoparticulate drug delivery systems in the treatment of range of diseases in modern therapeutics. Particular emphasis was given to the roles of these nanocarriers in overcoming the prompted limitations of conventional drug delivery systems.
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In response to the global outbreak caused by SARS-CoV-2, this article aims to propose the development of nanosystems for the delivery of hydroxychloroquine in the respiratory system to the treatment of COVID-19. Performed a descriptive literature review, using the descriptors "COVID-19", "Nanotechnology", "Respiratory Syndrome" and "Hydroxychloroquine", in the PubMed, ScienceDirect and SciElo databases. After analyzing the articles according to the inclusion and exclusion criteria, they were divided into 3 sessions: Coronavirus: definitions, classifications and epidemiology, pharmacological aspects of hydroxychloroquine and pharmaceutical nanotechnology in targeting of drugs. We used 131 articles published until July 18, 2020. Hydroxychloroquine seems to promote a reduction in viral load, in vivo studies, preventing the entry of SARS-CoV-2 into lung cells, and the safety of its administration is questioned due to the toxic effects that it can develop, such as retinopathy, hypoglycemia and even cardiotoxicity. Nanosystems for the delivery of drugs in the respiratory system may be a viable alternative for the administration of hydroxychloroquine, which may enhance the therapeutic effect of the drug with a consequent decrease in its toxicity, providing greater safety for implementation in the clinic in the treatment of COVID-19.
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Preprint
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Chapter
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The interaction between anticancer drugs and HSA may have a significant impact on the pharmacology and efficacy of drugs. Drugs change the binding properties of HSA by regulating the quenching mechanism, binding mode and binding affinity. In this study, the interactions of cisplatin (cDDP), HSA, and daphnoretin were elucidated by multi-spectroscopic analyses and docking simulation. Fluorescence quenching showed that cDDP could not change the static quenching mechanism of HSA-daphnoretin, but could enhance their binding affinity. Site competition experiments revealed that daphnoretin and cDDP both bound to site I, which was consistent with the results of molecular docking. Thermodynamic date indicated that cDDP and daphnoretin formed a more stable complex with HSA via hydrophobic, van der Waals interaction and hydrogen bond. Three-dimensional fluorescence and circular dichroism spectra showed that cDDP changed the conformation and micro-environment of HSA induced by daphnoretin. This work could provide valuable information for the binding properties and interaction among cDDP, daphnoretin and HSA, and put forward the possibility of using HSA as a multidrug carrier.
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Background Aim of this study was to prepare the hyaluronic acid and human serum albumin modified erlotinib nanoparticles (ERT-HSA-HA NPs) delivery system by a precipitation method. Methods ERT-HSA-HA NPs were characterized for physical properties, such as morphology and particle size, and in vitro drug release. Moreover, the cytotoxicity, cellular uptake, in vivo studies of ERT-HSA-HA nanoparticle were investigated and compared in A549 cells. Results The ERT-HSA-HA NPs showed spherical morphology, and their hydrodynamic diameter was 112.5±2.8 nm. The drug loading amount and encapsulation efficiency were 5.6% and 81.2%, respectively. After 3 months of storage, no dramatic change, such as visible aggregation, drug content changes, and precipitation, in the appearance of ERT-HSA-HA NPs occurred. In vitro release showed that the release of ERT from HSA-HA NPs was slow, without obvious burst effects at an early stage. In in vivo studies, ERT-HSA-HA NPs showed a superior antiproliferative effect on A549 cells, and the HA modification strategy can also facilitate the high-efficiency uptake of ERT-HSA NPs by A549 cells. Pharmacokinetic studies showed that the form of NPs could significantly extend the role of ERT in vivo (provided higher bioavailability). However, there was no significant difference in the pharmacokinetic parameters between ERT-HSA NPs and ERT-HSA-HA NPs after intravenous administration. In terms of in vivo antitumor activity, ERT-HSA-HA NP-treated mice showed a significantly suppressed tumor growth and no relapse after 30 d of treatment. Conclusion HA/HSA co-modified erlotinib albumin nanoparticles was expected to be a new strategy in the treatment of lung cancer.
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Background: Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury. Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations that consist of nanoparticles (NPs) have several advantages over other administration routes, and therefore, this study investigated the application of apigenin-loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery. Methods: Dry powder formulations of BSA-Api-NPs were prepared by spray drying and characterized by laser diffraction particle sizing, scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. The influence of dispersibility enhancers (lactose monohydrate and l-leucine) on the in vitro aerosol deposition using a next-generation impactor was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using the Franz cell apparatus. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH(⋅)) free radical scavenging assay. Results: The encapsulation efficiency and the drug loading were measured to be 82.61% ± 4.56% and 7.51% ± 0.415%. The optimized spray drying conditions were suitable to produce particles with low residual moisture content. The spray-dried BSA-Api-NPs possessed good aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose, and fine particle fraction. The aerodynamic properties were enhanced by leucine and decreased by lactose, however, the dissolution was reversely affected. The DPPH(⋅) assay confirmed that the antioxidant activity of encapsulated Api was preserved. Conclusion: This study provides evidence to support that albumin nanoparticles are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs are a novel delivery system against lung injury with potential antioxidant activity.
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The development of clinically acceptable albumin-based nanoparticle formulations for use in pulmonary drug delivery has been hindered by concerns about the toxicity of nanomaterials in the lungs combined with a lack of information on albumin nanoparticle clearance kinetics and biodistribution. In this study, the in vivo biocompatibility of albumin nanoparticles was investigated following a single administration of 2, 20, and 390μg/mouse, showing no inflammatory response (TNF-α and IL-6, cellular infiltration and protein concentration) compared to vehicle controls at the two lower doses, but elevated mononucleocytes and a mild inflammatory effect at the highest dose tested. The biodistribution and clearance of (111)In labelled albumin solution and nanoparticles over 48h following a single pulmonary administration to mice was investigated by single photon emission computed tomography and X-ray computed tomography imaging and terminal biodistribution studies. (111)In labelled albumin nanoparticles were cleared more slowly from the mouse lung than (111)In albumin solution (64.1±8.5% vs 40.6±3.3% at t=48h, respectively), with significantly higher (P<0.001) levels of albumin nanoparticle-associated radioactivity located within the lung tissue (23.3±4.7%) compared to the lung fluid (16.1±4.4%). Low amounts of (111)In activity were detected in the liver, kidneys and intestine at time points>24h indicating that small amounts of activity were cleared from the lungs both by translocation across the lung mucosal barrier, as well as mucociliary clearance. This study provides important information on the fate of albumin vehicles in the lungs, which may be used to direct future formulation design of inhaled nanomedicines. Copyright © 2015. Published by Elsevier B.V.
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The present study was an attempt to develop galactosylated albumin nanoparticles of Simvastatin for treatment of hypercholesterolemia. By developing the galactosylated nanoparticulated delivery, the required action of the drug at the target site at the liver can be provided. The advantage of targeting helps to reduce the systemic side effects that may occur due to the distribution of the drug to the other organs and thus helps in maintaining the required concentration of drug at the desired site. The galacotsylated albumin nanoparticles were prepared for the selective delivery of a Simvastatin to the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) the rate-limiting enzyme in the pathway of cholesterol biosynthesis that is particularly presents on hepatocytes. The asialoglycoprotein receptor (ASGP-R) which is particularly presents on mammalian hepatocytes can be utilize for active targeting by using its natural and synthetic ligands. By utilizing this receptors can provides a unique means for the development of liver-specific carriers, such as liposomes, recombinant lipoproteins, and polymers for drug or gene delivery to the liver, especially to hepatocytes. These receptors recognize the ligands with terminal galactose or N-acetylgalactosamine residues, and endocytose the ligands for an intracellular degradation process. The albumin nanoparticles (NPs) were prepared by using desolvation method and efficiently conjugated with galactose. Various parameters such as particle size, zeta potential, percentage entrapment efficiency and drug loading efficiency, percentage yield, in-vitro drug release were determined. The size of nanoparticles (both plain and coated NPs) was 200 and 250 nm. The zeta potential of plain nanoparticles was -3.61 and that of galactose-coated nanoparticles was 64.1. The maximum drug content was in between 79.98% to 79.8 % respectively in plain, and galactose coated nanoparticles while the maximum entrapment efficiency was 70.10% and 71.03% in plain and coated nanoparticles. It was found that coating of nanoparticles increases the size of nanoparticles.
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The evaluation of the effect of saline aqueous media in the aggregation of colloidal gold nanoparticles (AuNP) suspensions has been followed by means of both dynamic light scattering and UV–Vis spectroscopy techniques. A wide range of ionic strengths from 0 to 1 M has been covered for suspensions of AuNPs with a hydrodynamic radius of 6.5 nm. The growth of the clusters over time is described by a power law whose exponent varies with the ionic strength. Two main aggregation regimes are found in qualitative agreement with predictions of the DLVO theory. At low ionic strength, AuNPs form small aggregates that are long-term stable. When a critical electrolyte concentration is exceeded, big clusters are formed rapidly and then colloidal suspension becomes unstable and precipitation occurs. That so-called critical coagulation concentration was estimated by analyzing the time evolution of both the nanoparticle size (determined by DLS) and the plasmon peak (determined by UV–Vis spectroscopy), thus showing the validity of both techniques for such a purpose. The stability is also studied in terms of the zeta potential which approaches zero when salt concentration is above the critical coagulation concentration.
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Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and efficacy and ultimately altering the drug's pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used in clinical settings as a drug delivery system due to its potential for improving targeting while decreasing the side effects of drugs. It is thus of great importance from the viewpoint of pharmaceutical sciences to clarify the structure, function, and properties of HSA-drug complexes. This review will succinctly outline the properties of binding site of drugs in IIA subdomain within the structure of HSA. We will also give an overview on the binding characterization of interactive association of drugs to human serum albumin that may potentially lead to significant clinical applications.
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Bevacizumab-loaded nanoparticles (B-NP) were prepared by a desolvation process followed by freeze-drying, without any chemical, physical or enzymatic cross-linkage. Compared with typical HSA nanoparticles cross-linked with glutaraldehyde (B-NP-GLU), B-NP displayed a significantly higher mean size (310 nm vs. 180 nm) and a lower negative zeta potential (-15 mV vs. -36 mV). On the contrary, B-NP displayed a high payload of approximately 13% when measured by a specific ELISA, whereas B-NP-GLU presented a very low bevacizumab loading (0.1 μg/mg). These results could be related to the inactivation of bevacizumab after reacting with glutaraldehyde. From B-NP, bevacizumab was released following an initial burst effect, proceeded by a continuous release of bevacizumab at a rate of 6 μg/h. Cytotoxicity studies in ARPE cells were carried out at a single dose up to 72 hours and with repeated doses over a 5-day period. Neither bevacizumab nor B-NP altered cell viability even when repeated doses were used. Finally, B-NP were labeled with 99mTc and administered as eye drops in rats. 99mTc-B-NP remained in the eye for at least 4 hours while 99mTc-HSA was rapidly drained from the administration point. In summary, HSA nanoparticles may be an appropriate candidate for ocular delivery of bevacizumab.
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As a natural polymer, albumin is well-received for being nontoxic, nonimmunogenic, biodegradable and biocompatible. Together with its targeting potential on specific cells, albumin-based nanoparticles appear as an effective carrier for various therapeutics. In recent years, there has been an increasing number of studies investigating the use of albumin-based nanoparticles across different administration routes. Although each route and target tissue presents a distinct anatomical and physiological profile that demands specific consideration, pharmaceuticals could still be delivered effectively via albumin-based nanoparticles. Therefore, this review discusses the features that warrant such applications across various delivery routes and explores their possibilities in other administration routes. The challenges associated with its use will also be elaborated to provide a holistic consideration to realise their clinical potentials.
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Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects. Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects, including cough and bronchospasm. Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy. Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers. However, the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs. Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles. This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers.
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Nanoparticle vaccine delivery platforms are a promising technology for enhancing vaccine immunogenicity. Protein nanoparticles (PNPs), made entirely from antigen, have been shown to induce protective immune responses against influenza. However, the fundamental mechanisms by which PNPs enhance component protein immunogenicity are not understood. Here, we investigate the role of size and coating of model ovalbumin (OVA) PNPs on particle uptake and trafficking, as well as on inflammation and maturation factor expression in dendritic cells (DCs) in vitro. OVA PNPs enhance antigen uptake in a size-independent manner, and experience attenuated endosomal acidification as compared to soluble OVA. OVA PNPs also trigger Fc receptor upregulation. Expression of cytokines IL-1β and TNF-α were PNP size- and coating-dependent, with small (∼270 nm) nanoparticles triggering greater inflammatory cytokine production than large (∼560 nm) particles. IL-1β expression by DCs in response to PNP stimulation implies activation of the inflammasome, a pathway known to be activated by certain types of nanoparticulate adjuvants. The attenuated acidification and pro-inflammatory profile generated by PNPs in DCs demonstrate that physical biomaterial properties can modulate dendritic cell-mediated antigen processing and adjuvancy. In addition to nanoparticles' enhancement of DC antigen uptake, our work suggests that vaccine nanoparticle size and coating are uptake-independent modulators of immunogenicity.
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The deep lungs provide an efficient pathway for drugs to transport into the systemic circulation, as the extremely large surface area and thin epithelial membrane enable rapid drug transport to the blood stream. To penetrate into the deep lungs, aerosol particles with aerodynamic diameters of 1-3 μm are optimal. Large porous hollow particles (LPHPs) can achieve this aerodynamic size range through enhanced porosity within the particles (typically < 0.4 g/cm3), which aerodynamically balances the large particle size (> 5 μm, up to 30 μm). The physical properties of these particles provide some key advantages compared to their small, nonporous counterparts through enhanced dispersibility, efficient deep lung deposition, and avoidance of phagocytic clearance. This review highlights the potential of LPHPs in pulmonary delivery of systemic drugs, with a focus on their critical attributes and key formulation aspects. In addition, three examples of LPHPs under development are presented to emphasize the potential of this technology to treat systemic diseases.
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Tacrolimus (Tac) is an immunosuppressant that inhibits translocation of nuclear factor of activated T cells and has therapeutic potential for pulmonary fibrosis. Here, we investigated the therapeutic efficacy of a sustained-release type inhaled Tac formulation for treating bleomycin-induced pulmonary fibrosis. Inhalation has many meaningful advantages over injections, such as improved patient compliance, safety, and therapeutic effect. To this end, we fabricated inhalable albumin nanoparticles with bound Tac (Tac Alb-NPs) at a daily therapeutic dose (60 μg/mouse) using a high-pressure homogenizer via nanoparticle albumin-bound technology. The Tac Alb-NPs were spherical, ∼182.1 ± 28.5 nm in size, with a zeta potential of −34.5 ± 0.3 mV, and the Tac incorporation efficiency was as high as ∼85.3%. The bound tacrolimus was released gradually from Tac Alb-NPs for ∼24 h, which was sufficient time for pulmonary delivery. Most of all, the inhaled Tac Alb-NPs displayed remarkable anti-fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from intraperitoneal administration of Tac (60 μg/mouse) based on histopathological results (hematoxylin and eosin and Masson’s trichrome staining). Furthermore, the inhaled Cy5.5-labelled Tac Alb-NPs were visualized throughout the lungs of mice for ∼48 h, indicating direct exposure to fibrotic tissues in lung lesions. In conclusion, Tac Alb-NPs offer great potential as an inhalation delivery formulation for treating pulmonary fibrosis. Additionally, these NPs would be particularly useful as an effective and safe prototype for delivering practically insoluble therapeutic agents into the lungs.
Book
In complex macromolecules, minor modifications can generate major changes, due to self-assembling capacities of macromolecular or supramolecular networks. Controlled Drug Delivery highlights how the multifunctionality of several materials can be achieved and valorized for pharmaceutical and biopharmaceutical applications. Topics covered in this comprehensive book include: the concept of self-assembling; starch and derivatives as pharmaceutical excipients; and chitosan and derivatives as biomaterials and as pharmaceutical excipients. Later chapters discuss polyelectrolyte complexes as excipients for oral administration; and natural semi-synthetic and synthetic materials. Closing chapters cover protein-protein associative interactions and their involvement in bioformulations; self-assembling materials, implants and xenografts; and provide conclusions and perspectives. • Offers novel perspectives of a new concept: how minor alterations can induce major self-stabilization by cumulative forces exerted at short and long distances • Gives guidance on how to approach modifications of biopolymers for drug delivery systems and materials for implants • Describes structure-properties relationships in proposed excipients, drug delivery systems and biomedical materials.
Chapter
This chapter presents albumin binding sites. The binding process to albumin has physiological significance in transport, modulation, inactivation of metabolite, and drug activities. It also acts as a protective device in binding and inactivation of potential toxic compounds to which the body is exposed. Forces available for the attachment of ligands to proteins are of several types, namely, electrostatic, fluctuating charges, hydrogen bonding, and apolar bonding. Some proteins bind anions, some do not. Compact proteins, supporting interiors of low dielectric constant, with positive charged groups, are potentially good anionic binders. This holds for albumin from almost all sources. Albumin binds most anions, independent of the hydrophobic character of the ligand side group, although if the latter is appreciable it clearly increases the affinity of attachment.
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Docetaxel (DTX) is a widely used chemotherapeutic agent with very low water solubility. Conjugation of DTX to Human Serum Albumin (HSA) is an effective way to increase its water solubility. Attachment of Folic Acid (FA) or biotin as targeting moieties to DTX-HSA conjugates may lead to active targeting and specific uptake by cancer cells with overexpressed FA or Biotin receptors. In this study, FA or Biotin molecules were attached to DTX-HSA conjugates by two different methods. In one method FA or Biotin molecules were attached to remaining NH2 residues of HSA in DTX-HSA conjugate by covalent bonds. In the second method HSA-FA or HSA-Biotin conjugates were synthesized separately and then combined by DTX-HSA conjugate in proper ratio to prepare nanoparticles containing DTX-HSA plus HSA-FA or HSA-Biotin. Cell viability of different nanoparticle were evaluated on MDA-MB-231 (folate receptor positive), A549 (folate receptor negative) and 4T1 (biotin receptor positive) and showed superior cytotoxicity compared with free docetaxel (Taxotere(®) ). In vivo studies of DTX-HSA-FA and DTX-HSA-Biotin conjugates in BULB/c mice, tumorized by 4T1 cell line, showed the conjugates prepared in this study were more powerful in the reduction of tumor size and increasing the survival rate when compared to free docetaxel. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Increasing rates of antimicrobial resistance have left a significant gap in the standard antimicrobial armament. Nanotechnology holds promise as a new approach to combating resistant microbes. Chitosan, a form of deacetylated chitin, has been used extensively in medicine, agriculture and industry due to its ease of production, biocompatibility and antimicrobial activity. Chitosan has been studied extensively as a main structural component and additive for nanomaterials. Specifically, numerous studies have demonstrated its potent microbicidal activity and its efficacy as an adjuvant to vaccines, including mucosally administered vaccines. In this review, we present fundamental information about chitosan and chitosan nanoparticles as well as the most recent data about their antimicrobial mechanism and efficacy as a nanotechnology-based drug delivery system.
Article
In the present work, ovalbumin (OVA) solutions (10g/L, 50mM NaCl, pH 7.5) were heat-treated at 75, 80 and 85°C (namely, OVA-75, OVA-80 and OVA-85, respectively), from 0 to 25min. OVA nanoparticles (OVAn) around 100nm were obtained. For 3min of heat treatment, OVAn sizes increased with temperature, but for a heating time longer than 10min, OVA-75 showed the highest size values. OVAn surface hydrophobicity increased 6-8 folds in comparison with native OVA and wavelength blue shifts of 25-30nm in maximum fluorescence intensity were registered. These results suggest that buried hydrophobic residues were exposed to the aqueous medium. Binding experiments with linoleic acid (LA) as polyunsaturated fatty acid (PUFA) model were carried out. Firstly, binding ability of OVAn was determined from LA titration curves of intrinsic fluorescence measurements. OVA-85 at 5min presented the highest binding ability and it was used for further binding properties studies (turbidity, particle size distribution - PSD - analysis and ζ-potential measurements). Turbidity measurement and PSD analysis showed that OVAn-LA nanocomplexes were formed, avoiding LA supramolecular self-assembly formation. The union of LA to OVAn surface confers them significant lower ζ-potential and larger size. Hence, fluorescence and ζ-potential results showed that LA would bind to OVAn by mean of hydrophobic interactions. Information derived from this work could be important to potentially use OVAn as PUFA vehiculization with applications in several industrial sectors (food, pharmaceutical, cosmetics, etc.). Copyright © 2015 Elsevier B.V. All rights reserved.
Article
Direct pulmonary delivery of anti-cancer agents is viewed as an effective way of treating lung cancer. Here, we fabricated inhalable nanoparticles made of human serum albumin (HSA) conjugated with doxorubicin and octyl aldehyde and adsorbed with apoptotic TRAIL protein (TRAIL/Dox HSA-NP). The octyl aldehyde and doxorubicin endowed HSA with significant hydrophobicity that facilitated self-assembly. TRAIL/Dox HSA-NP was found to have excellent particle size (~340nm), morphology, dispersability, and aerosolization properties. TRAIL/Dox HSA-NP displayed synergistic cytotoxicity and apoptotic activity in H226 lung cancer cells vs. HSA-NP containing TRAIL or Dox alone. TRAIL/Dox HSA-NP was well deposited in the mouse lungs using an aerosolizer, and TRAIL and Dox-HSA were found to be gradually released over 3days. The anti-tumor efficacy of pulmonary administered TRAIL/Dox HSA-NP was evaluated in BALB/c nu/nu mice bearing H226 cell-induced metastatic tumors. It was found that the tumors of H226-implanted mice treated with TRAIL/Dox HSA-NP were remarkably smaller and lighter than those of mice treated with TRAIL or Dox HSA-NP alone (337.5±7.5; 678.2±51.5; and 598.9±24.8mg, respectively). Importantly, this improved anti-tumor efficacy was found to be due to the synergistic apoptotic effects of Dox and TRAIL. In the authors' opinion, TRAIL/Dox HSA-NP offers a potential inhalable anti-lung cancer drug delivery system. Furthermore, the synergism displayed by combined use of Dox and TRAIL could be used to markedly reduce doxorubicin doses and minimize its side effects. Copyright © 2014 Elsevier B.V. All rights reserved.
Article
Purpose Dry powder vaccine delivery via the pulmonary route has gained significant attention as an alternate route to parenteral delivery. In this study, we investigated bovine serum albumin (BSA) adsorbed poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL polymeric nanoparticles (NPs) within L-leucine (L-leu) microcarriers for dry powder inhalation. Methods NPs were prepared by oil-in-water single emulsion-solvent evaporation and particle size optimised using Taguchi’s design of experiment. BSA was adsorbed onto NPs at different ratios at room temperature. The NPs were spray-dried in aqueous suspension of L-leu (1:1.5) using a Büchi-290 mini-spray dryer. The resultant nanocomposite microparticles (NCMPs) were characterised for toxicity (MTT assay), aerosolization (Next Generation Impactor), in vitro release study and BSA was characterized using SDS-PAGE and CD respectively. Results NPs of size 128.50 ± 6.57 nm, PDI 0.07 ± 0.03 suitable for targeting lung dendritic cells were produced. BSA adsorption for 1 h resulted in 10.23 ± 1.87 μg of protein per mg of NPs. Spray-drying with L-leu resulted in NCMPs with 42.35 ± 3.17% yield. In vitro release study at 37°C showed an initial burst release of 30.15 ± 2.33% with 95.15 ± 1.08% over 48 h. Aerosolization studies indicated fine particle fraction (FPF%) dae < 4.46 μm as 76.95 ± 5.61% and mass median aerodynamic diameter (MMAD) of 1.21 ± 0.67 μm. The cell viability was 87.01 ± 14.11% (A549 cell line) and 106.04 ± 21.14% (16HBE14o- cell line) with L-leu based NCMPs at 1.25 mg/ml concentration after 24 h treatment. The SDS-PAGE and CD confirmed the primary and secondary structure of the released BSA. Conclusions The results suggest that PGA-co-PDL/L-leu NCMPs may be a promising carrier for pulmonary vaccine delivery due to excellent BSA adsorption and aerosolization behaviour.
Article
Pancreatic cancer is considered to be the deadliest of all cancers due to its poor prognosis and resistance to conventional therapies. In this study, the potential of hyaluronic acid functionalized and green fluorescent graphene quantum dot (GQD)-labeled human serum albumin nanoparticles for pancreatic cancer specific drug delivery and bioimaging was explored. GQDs with tunable fluorescence properties and biocompatibility have attracted much more interest in recent years as compared to their metal semiconductor counterparts. We adopted lawsone (2-hydroxy-1,4-naphthoquinone) as a novel reducing agent for the synthesis of quantum dots and, in addition to excellent fluorescence of the synthesized GQDs, a good quantum yield of [similar]14% was also obtained. Gemcitabine, the most preferred drug for pancreatic cancer treatment, was encapsulated in albumin nanoparticles, and it was observed that our nanoformulation significantly enhanced the bioavailability and sustained release property of the drug to pancreatic cancer cells in vitro. Moreover, the GQD-mediated bioimaging was excellent and enhanced the efficacy of our system as a drug delivery vehicle.
Article
Nanoparticles using albumin as particle matrix have entered the mainstream of drug delivery. It was reported that non-crosslinked albumin nanoparticles were unstable in circulation and could deliver drugs into tumor through gp60/SPARC pathway; in contrast, the delivery of drugs with stable nanoparticles was dependent on enhanced permeability and retention effect. Thus, it is questionable which kind of nanoparticles was more advantageous. Two versions of albumin-bound paclitaxel nanoparticles were prepared. In vitro, the non-crosslinked particles could rapidly disintegrate and the crosslinked was stable. The pharmacokinetics of both formulations was different especially at early time and the non-crosslinked particles were cleared rapidly. After non-crosslinked particle treatment paclitaxel had a tendency to accumulate into heart and kidney and following therapy with the crosslinked particles, paclitaxel was liable to be delivered into lung, spleen and liver. The delivery efficiency of paclitaxel into tumor following the non-crosslinked particle treatment was greater than that of the crosslinked (p<0.05), thus resulting in a considerably improved antineoplastic activity. Moreover, the non-crosslinked formulation was only slightly more toxic. It was concluded that the non-crosslinked formulation was more advantageous for the delivery of paclitaxel and our conclusion might be generalized to other lipophilic drugs delivered with albumin nanoparticles.
Article
Abstract Haloperidol (Hal) is a ligand that can target sigma 2 receptors over-expressed in non-small cell lung cancer. Hal targeted nanoparticles of bovine serum albumin (BSA) were prepared for pulmonary delivery of doxorubicin (DOX). The conjugation was confirmed by Fourier transform infrared spectroscopy (FTIR) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopic methods. Nanoparticles were prepared by desolvation method from BSA-Hal and were loaded with DOX. They were characterized for their morphology, particle size, zeta potential, drug loading and release efficiency. The optimized nanoparticles were spray-dried using trehalose, l-leucin and mannitol as dry powder inhaler (DPI) in different inlet temperatures between 80 and 120 °C. The obtained nanocomposites were characterized for their aerodynamic diameter, specific surface area (cm(2)/g) and fine particle fraction (FPF) by a Cascade Impactor device. The optimized nanoparticles showed particle size of 218 nm, zeta potential of -25.4 mV, drug entrapment efficiency of 89% and release efficiency of 56% until 2 h. After spray drying of these nanoparticles, the best results were obtained from mannitol with an inlet temperature of 80 °C which produced a mean aerodynamic diameter of 4.58 μm, FPF of 66% and specific surface area of 6302.99 cm(2)/g. The obtained results suggest that the designed DPI could be a suitable inhaler for targeted delivery of DOX in pulmonary delivery.
Article
Albumin nanoparticles are attractive drug delivery systems as they can be prepared under soft conditions and incorporate several kinds of molecules. The aim of this study was to upscale the desolvation process for preparing bovine serum albumin (BSA) nanoparticles using a membrane contactor. At a first step, the BSA nanoparticles were prepared at small scale using a syringe pump. BSA nanoparticles of 139 nm in size, with a polydispersity index of 0.046 were obtained at the optimal conditions: pH 8.2, 100 mg.mL(-1) BSA albumin solution (2 mL), 1 mL.min(-1) flowrate of ethanol addition (8 mL). The upscaling with a membrane contactor was achieved by permeating ethanol through the pores of a Shirasu Porous Glass (SPG Technology Co., Japan) membrane and circulating the aqueous phase tangentially to the membrane surface. By increasing the pressure of the ethanol from 1 to 2.7 bars, a progressive decrease in nanoparticle size was obtained with a high nanoparticles yield (around 94-96%). In addition, the flowrate of the circulating phase did not affect the BSA nanoparticle characteristics. At the optimal conditions (pH 8.2, 100 mg.mL(-1) BSA albumin solution, pressure of ethanol 2.7 bars, flowrate of the circulating phase 30.7 mL.s(-1)), the BSA nanoparticles showed similar characteristics to those obtained with the syringe pump. Large batches of BSA nanoparticles were prepared up to 10 g BSA. The BSA nanoparticles were stable at least during 2 months at 4° C and their characteristics were reproducible. It was then concluded that the membrane contactor technique could be a suitable method for the preparation of albumin nanoparticles at large scale with properties similar to that obtained at small scale.
Article
In polymeric nanoparticle preparation, despite similar conditions, large fluctuations in particle size distributions are usually observed. Herein, we demonstrate that the intermittent addition of a desolvating agent can improve reproducibility in the preparation of polymeric bovine serum albumin (BSA) nanoparticles. Using this modification, BSA nanoparticles of controlled size can be manufactured with narrow particle size distributions. In our study, ethanol as a desolvating agent was added intermittently to 1% BSA solutions at different pHs with stirring at 700rpm. The effect of the preparation parameters on size and optical density of the fabricated nanoparticles were studied. The average particles sizes of BSA nanoparticles prepared at pH values of 6, 7 and 9 were approximately 100, 200 and 300nm, respectively. As ethanol addition increased, desolvation of BSA molecules resulted in formation of loose-structured particles with pH-dependent size. Beyond that, only particle density increased, but size remained unchanged with further addition of ethanol. Consistently uniform particle size distribution was achieved by adding ethanol intermittently.
Article
Tanshinone IIA is a good candidate for treating cerebral ischemia, but its short half-life and poor permeability across the blood-brain-barrier (BBB) limit its curative efficacy. In this study, we successfully developed cationic bovine serum albumin-conjugated tanshinone IIA PEGylated nanoparticles (CBSA-PEG-TIIA-NPs). A cerebral ischemia rat model was established to evaluate the treatment efficacy and protective mechanism of CBSA-PEG-TIIA-NPs. CBSA-PEG-TIIA-NPs showed the mean particle size 118 ± 14 nm with drug loaded ratio and encapsulation efficiency 5.69 ± 0.6% and 83.2 ± 2.6%, respectively. The pharmacokinetics demonstrated that CBSA-PEG-TIIA-NPs could significantly prolong circulation time and increase plasma concentration compared with intravenously administrated TIIA solution. The biodistribution and brain uptake study confirmed that CBSA-PEG-TIIA-NPs possessed better brain delivery efficacy with a high accumulation in brain. CBSA-PEG-TIIA-NPs obviously ameliorated infarct volume, neurological deficit and histopathological severity. Treatment with CBSA-PEG-TIIA-NPs markedly inhibited the levels of the MPO, TNF-α, IL-1β and IL-6. Furthermore, CBSA-PEG-TIIA-NPs significantly decreased the mRNA expressions of iNOS and p38MAPK, upregulated PPARγ expression, and inhibited the protein levels of iNOS, GFAP and p38MAPK phosphorylation. These results demonstrated that CBSA-PEG-TIIA-NPs possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and neuronal signal pathways involved in cerebral ischemia.
Article
The interactions of alpha-lactalbumin and bovine serum albumin (BSA) with beta-lactoglobulin in mixed-protein gel systems were investigated by dynamic oscillation rheology and aggregation rates. BSA and alpha-lactalbumin were found to contribute to the storage modulus (G') of mixed-protein gels made primarily with beta-lactoglobulin. Gels made with beta-lactoglobulin alone, or combinations of alpha-lactalbumin and beta-lactoglobulin, had similar transitions and ultimate values for G'. In contrast, the rheological transitions and properties of gels made with mixtures of beta-lactoglobulin and BSA were dependent on the ratio of proteins in the mixture. Second-order aggregation rate constants of alpha-lactalbumin, beta-lactoglobulin, and BSA heated alone at 80-degrees-C were in the order BSA much greater than beta-lactoglobulin > alpha-lactalbumin. The aggregation rate of alpha-lactalbumin increased when heated in combination with beta-lactoglobulin, suggesting a coaggregation of proteins. These results indicate that rheological properties of whey protein gels can be altered by changing the ratios of constitutive proteins.
Article
The size effect of nanomaterials is of major interest, since it may affect their bioavailability and toxicity. In this study, bovine serum albumin (BSA) nanoparticles were prepared using a modified desolvation method. Bare BSA nanoparticles and calcium (Ca)-loaded BSA nanoparticles were fabricated at the targeted sizes, 100, 400, and 800 nm. The mean diameters of the prepared BSA nanoparticles were 125, 393, and 713 nm; those of the Ca-BSA nanoparticles were 260, 353, and 919 nm. The surface-area-to-volume-ratios of the prepared BSA nanoparticles were 4.82, 1.53, and 1.03 nm−1; those of the Ca-BSA nanoparticles were 2.34, 1.72, and 0.90 nm−1. The size and the surface-area-to-volume-ratio of the BSA nanoparticles were controlled by adjusting BSA concentration, pH, and NaCl content, which affected the coagulation of the BSA molecules. The surface-area-to-volume-ratio is a more useful parameter than the mean diameter of particles for comparing effectiveness of nanoparticles.Research highlights► Nanoparticles of a controlled size are important to ascertain size effect in food. ► Difference in manufacturing processes affects particle properties. ► Different-size similar-surface particles are good tools to study size effect. ► Size-controlled BSA nanoparticles are prepared by similar manufacturing processes. ► Size-controlled BSA nanoparticles prepared are useful as standard materials.
Article
The complete amino acid sequence of hen ovalbumin, comprising 385 residues, has been determined. The sequence was deduced from the 17 cyanogen bromide fragments and from peptides derived by digestion with a number of proteolytic enzymes. The molecular weight of the polypeptide chain of ovalbumin is 42699. Ovalbumin has four sites of postsynthetic modification; in addition to the acetylated N terminus, the carbohydrate moiety is located at Asn-292, and the two phosphorylated serines are at residues 68 and 344. The ‘signal sequence’ of ovalbumin is between residues 234 and 252. The heptapeptide released during the conversion of ovalbumin to plakalbumin by subtilisin digestion corresponds to residues 346–352. The hen ovalbumin polymorphism characterised by an Asn–>Asp replacement results from a mutation at residue 311. The amino acid sequence of ovalbumin deduced from these amino acid sequence studies is in complete agreement with the sequence of mRNA determined by McReynolds et al. [Nature (Lond.) 273, 723–728 (1978)].
Article
In this review the current knowledge of protein degradation during preparation, storage and release from poly(lactic-co-glycolic acid) (PLGA) microparticles is described, as well as stabilization approaches. Although we have focussed on PLGA microparticles, the degradation processes and mechanisms described here are valid for many other polymeric release systems. Optimized process conditions as well as stabilizing excipients need to be used to counteract several stress factors that compromise the integrity of protein structure during preparation, storage, and release. The use of various stabilization approaches has rendered some success in increasing protein stability, but, still, full preservation of the native protein structure remains a major challenge in the formulation of protein-loaded PLGA microparticles.
Article
An analysis of the intrinsic tryptophan fluorescence of human serum albumin (HSA) confirms that the denaturation of HSA by sodium dodecyl sulfate takes place in two stages for different pH levels: the first is the disintegration of globules and the second is the complete unfolding of the amino acid chain of HSA. At pH levels below the isoelectric point (pI 4.7) of HSA, denaturation proceeds through both stages, but when the pH is above pI, denaturation ceases in the first stage.
Article
Unsaturated groups were introduced onto proteins in order to produce macromers that are able to undergo radical polymerisation. The initial protein used was bovine serum albumin (BSA) because it is biodegradable, biocompatible and easily available. Methacrylic groups were introduced onto BSA by reaction with methacrylic anhydride at controlled pH and temperature. The experimental conditions allowed the protein to be kept water-soluble. This water-solubility of the derivatised protein was essential when realising spherical polymeric microparticles via reverse phase suspension copolymerisation with N,N-dimethyacrylamide (DMAA). During the derivatisation, the insertion of the polymerisable groups affects only the sterically-available chemical functions of the native protein. Therefore, chain growth during the copolymerisation process involves only these groups, achieving a polymeric network around a structurally unmodified protein. The polymeric systems show high water affinity, ascribable to the hydrophilic properties of BSA. We have demonstrated that the achievement of the spherical form during the polymerisation depends on two factors: the degree of derivatisation of BSA, and the weight/weight (w/w) ratio of the protein to the comonomer. The beads obtained were characterised by Fourier transform IR spectrophotometry, particle size distribution analysis, and scanning electron microscopy (SEM). The samples investigated showed a remarkable affinity for water and a high swelling capacity. These properties depend upon the degree of derivatisation of BSA and on the percentage of DMAA in the copolymerisation mixture. In this paper we describe the starting materials and the experimental conditions used to prepare protein hydrogels by radical copolymerisation, which are intended for use in pharmaceutical and biomedical applications.
Article
The paper examines the progress made in nanotechnology development since 2000, achievements at ten years, and opportunities in research, education, innovation and societal outcomes by 2020 worldwide. KeywordsNanoscale science and engineering–Research, education and innovation–Forecast–Governance–Societal implications–International perspective
Article
Serum albumin (SA) is the most abundant plasma protein in mammals. SA is a multifunctional protein with extraordinary ligand binding capacity, making it a transporter molecule for a diverse range of metabolites, drugs, nutrients, metals and other molecules. Due to its ligand binding properties, albumins have wide clinical, pharmaceutical, and biochemical applications. Albumins are also allergenic, and exhibit a high degree of cross-reactivity due to significant sequence and structure similarity of SAs from different organisms. Here we present crystal structures of albumins from cattle (BSA), horse (ESA) and rabbit (RSA) sera. The structural data are correlated with the results of immunological studies of SAs. We also analyze the conservation or divergence of structures and sequences of SAs in the context of their potential allergenicity and cross-reactivity. In addition, we identified a previously uncharacterized ligand binding site in the structure of RSA, and calcium binding sites in the structure of BSA, which is the first serum albumin structure to contain metal ions.
Article
Doxorubicin (DXR) commonly used in cancer therapy produces undesirable side effects such as cardiotoxicity. To minimize these, attempts have been made to couple the drug with dextran (DEX) and then to encapsulate this drug conjugate in hydrogel nanoparticles. By encapsulation of the drug conjugate in biodegradable, biocompatible long circulating hydrogel nanoparticles, we further improved the therapeutic efficacy of the conjugate. The size of these nanoparticles as determined by quasi-elastic light scattering, was found to be 100±10 nm diameter, which favors the enhanced permeability and retention effect (EPR) as observed in most solid tumors. The antitumor effect of these DEX–DXR nanoparticles, was evaluated in J774A.1 macrophage tumor cells implanted in Balb/c mice. The in vivo efficacy of these nanoparticles as antitumor drug carriers, was determined by tumor regression and increased survival time as compared to drug conjugate and free drug. These results suggest that encapsulation of the conjugate in nanoparticles not only reduces the side effects, but also improves its therapeutic efficacy in the treatment of solid tumors.
Article
Biodegradable hydrogel nanoparticles were prepared from glycidyl methacrylate dextran (GMD) and dimethacrylate poly(ethylene glycol) (DMP). GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine (DMAP) using dimethylsulfoxide (DMSO) as an aprotic solvent. DMP was synthesized from poly(ethylene glycol) (PEG) and methacryloyl chloride. GMD/DMP (abbreviated as DP) hydrogel was prepared by radical polymerization of GMD and DMP using ammonium peroxydisulfate (APS) as an initiator and UV curing. DP hydrogel nanoparticles were obtained by diafiltration method using DMSO solution. The GMD and DMP were characterized by fourier transform infrared spectroscopy. Fluorescence probe technique was used to investigate the self-assembly of DP in water using pyrene as a hydrophobic probe. The critical association concentration (CAC) was determined to be 5.6×10−2 g/l. The shape of DP hydrogel nanoparticles was spherical when observed by transmission electron microscope (TEM). The size range of DP hydrogel nanoparticles was about 20∼50 nm. The hydrodynamic size of DP hydrogel nanoparticles was measured by photon correlation spectroscopy (PCS) and gradually increased with time in PBS (0.1 M, pH 7.4). Drug release study was performed using clonazepam (CNZ) as a hydrophobic model drug. In vitro release rate of CNZ from the DP hydrogel nanoparticles was dependent on the existence of dextranase and the pH of the release medium.