[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to improve the transdermal permeation of sulfadiazine sodium, employing synergistic combination of surfactants (in the form of niosomes) and additives with different number of hydroxylic groups, (following referred to as "alcohol"), as component of the bilayer. In particular the effect of different concentration of each alcohol (ethanol, propylene glycol or glycerol, from 5%, to 40% v/v) on niosomes size and distribution, drug entrapment efficiencies and ex vivo drug percutaneous permeation were evaluated, identifying formulations giving the best performances. The findings revealed that the presence of alcohol critically affect the physico-chemical properties of niosomes, with regards to dimensions, drug encapsulation and permeation. Vesicular size increased with the amount of alcohol and at the same alcohol concentration, follow the sequence ethanol>propylene glycol>glycerol. Loaded niosomes were larger than empty ones. Low E% values were found for ethanol, even less in propylene glycol and glycerol based samples, confirming that the chemical structure of the alcohol and its physico-chemical properties, affected the sulfadiazine entrapment efficiency. The comparative evaluation of percutaneous permeation profiles showed that the cumulative amount of permeated drug increases with alcohol concentration up to 20% v/v. Higher concentration (40% v/v) resulted in a strong decrease of the potential skin permeation. Best performances were obtained with glycerol. In all cases ex vivo sulfadiazine percutaneous permeations are controlled and improved respect to the corresponding free drug solutions and traditional niosomes used as controls.
Colloids and surfaces B: Biointerfaces 09/2014; · 4.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The synthesis of an innovative delivery system for targeted cancer therapy which combines the drug controlled release ability of Molecularly Imprinted Polymers (MIPs) with magnetic properties of magnetite is described herein. In the present study, an easy and smart synthetic strategy, involving new engineered precipitation photo-polymerization, was developed with the aim to obtain Magnetic Molecularly Imprinted Polymers (MMIPs) for 9H-carbazole derivative sustained delivery in cancer treatment. Both in vitro drug release and cytotoxicity studies on different cancer cell lines, such as HeLa and MCF-7, were performed in order to evaluate the controlled release ability and the potential application as a drug carrier in targeted cancer therapy. The synthesized polymeric materials have shown not only good selective recognition and controlled release properties, but also high magnetic responding capacity. The performed cytotoxicity studies highlighted the high inhibitory activity against the tested cell lines due to a dramatic growth arrest, compared to controls, by triggering apoptosis. These results clearly indicate the potential application of synthesized MMIPs as a magnetic targeted drug delivery nanodevice.
[Show abstract][Hide abstract] ABSTRACT: The objective of this research was to study the effect of diclofenac sodium compartmentalization on the physico-chemical properties (such as size, drug entrapment efficiency and percutaneous permeation across rabbit skin) of niosomal vesicles used as carriers. Niosomes were prepared starting from nonionic commercial surfactants belonging to the class of Polysorbates and Pluronics: mixtures of Span 60/F127 and Tween 60/F127 at different ratios were used to obtain vesicles and all formulations were compared in terms of dimensions, morphology, polydispersity index and entrapment efficiency. Moreover, the enhancing effect of niosomes on the ex vivo percutaneous penetration of diclofenac sodium was investigated using Franz-type diffusion chambers and compared to that obtained by using the corresponding drug solution. Results demonstrated that niosomes were spherical and homogeneous in shape. Their size was found to be dependent on the hydrophile-lipophile balance of the surfactant mixture: increasing hydrophobicity resulted in smaller vesicles. Drug incorporation led to a significant variation in vesicle size dependently from the compartment in which the drug was located. The permeation of diclofenac from free solution used as control was found to be lower respect to that obtained for all niosomal formulations, that can be considered as percutaneous permeation enhancers. In particular, the results indicated that the highest cumulative amounts of diclofenac permeated across rabbit skin after 24 h were obtained by formulations in which the drug was located in the aqueous core.
[Show abstract][Hide abstract] ABSTRACT: The most exciting promise of cell micro-bioreactors is their expected ability to reproduce specific aspects of physiological environments in vitro, singularly or in combination, and to perform advanced biological studies to unravel novel interaction mechanisms; but this challenge is formidable. Moreover, the use of microfluidics is limited by the difficulty to adapt standard tissue culture protocols to miniaturised biochips and by the need of bulky external equipment such as liquid pumping systems. Here, we introduce an original microfluidic gradient generator for culturing cells in closed microchambers, based on: (1) automatic cell valving, (2) hydrostatic-pressure pumping, and (3) on-chip liquid reservoirs. The biochip is designed to be fully compatible with standard biological procedures and to operate with no external control units or cumbersome ancillary components. Remarkably, the use of integrated liquid reservoirs prevents air bubble formation and associated channel clogging. We detail the rationale behind the fluidic design, simulate and measure the chip fluid-dynamics by finite element simulations and microflow velocimetry, respectively. We finally exploit our chip to study the kinetics of an anti-cancer molecule, the catechin–dextran conjugate, on HeLa cells, demonstrating a very fast action. We argue that the presented fluidic concept and architecture are not limited to the present realization, but can be easily applied to other chip geometries and adapted to a number of biological studies.
[Show abstract][Hide abstract] ABSTRACT: Abstract The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans.
[Show abstract][Hide abstract] ABSTRACT: Abstract In recent years, antioxidants have gained great importance because of their potential use in food, pharmaceutical, and cosmetic industries. This interest is rooted in the cumulative evidence connecting active oxygen and free radicals with numerous human degenerative disorders such as cardiovascular diseases, cancer, aging, and atherosclerosis. Polyphenols are the major class of antioxidant able to reduce the oxidative damages of lipids, proteins, enzymes, carbohydrates, and DNA in living cells and tissues. Among the realm of polyphenol compounds, polyphenol conjugates have been proposed as innovative materials which, by combining the advantageous properties of both the components, can increase the efficiency of antioxidants and their range of application in nutritional and biomedical fields. This work is an overview of the different class of polyphenol conjugates, which will be analyzed in terms of nutritional and biological properties, showing how these bio-conjugates will positively affect the human health.
Critical reviews in food science and nutrition. 05/2014;
[Show abstract][Hide abstract] ABSTRACT: Niosomes are vesicular systems composed of surfactant molecules, claimed to be used as drug delivery carriers thanks to their physico-chemical and biological properties. The aim of this work was to design niosomes obtained with a surfactant synthesized from glucuronic acid. Doxorubicin and 5FU were used as model drugs. Niosomes were prepared with different ratios between surfactant and cholesterol, and characterized in terms of size, morphology, drugs entrapment efficiency and in vitro releases, to identify the optimal formulation to be used in pharmaceutical fields. In addition, the hemolytic activity of all formulations have been also evaluated. Results showed that dodecylglucuronamide surfactant was able to produce vesicular systems with or without the presence of cholesterol. Niosomes resulted regular in size and shape and they have been found to encapsulate and release in a controlled manner both doxorubicin and 5-fluorouracil. Hemolytic tests showed that the capability of disrupting erythrocyte only depend on the size of colloidal aggregates. Finally, our formulations could be potentially used as antitumoral delivery systems in anticancer therapy.
[Show abstract][Hide abstract] ABSTRACT: The use of biologics, polymers, silicon materials, carbon materials, and metals has been proposed for the preparation of innovative drug delivery devices. One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materials coupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptake, stability, electromagnatic, and magnetic behavior). The applicability of polymer-carbon nanotubes composites in drug delivery, with particular attention to the controlled release by composites hydrogel, is being extensively investigated in the present review.
BioMed research international. 01/2014; 2014:825017.
[Show abstract][Hide abstract] ABSTRACT: A new approach for the synthesis of hydrogel films with thermo-sensitive enzymatic activity is reported. Pepsin (PEP) was covalently immobilized on thermo-responsive hydrogels by radical polymerization in the presence of N-isopropylacrylamide and poly-(ethylene glycol) dimethacrylate 750, acting as functional monomer and crosslinking agent, respectively. Hydrogels showing lower critical solution temperatures between 32.9 and 36.1°C were synthesized by UV-irradiation of reaction batches differing in the PEP/monomers ratio. The derivatization degree of the hydrogels was expressed as mg of PEP per gram of matrix and found to be in the range of 6 to 11% as assessed by Lowry method. Scanning electron microscopy analysis and water affinity evaluation allowed to highlight the porous morphology and thermo-responsivity of hydrogels as a function of temperature. Using bovine serum albumin as a substrate, kinetics parameters were determined by Lineweaver–Burk plots and the catalyst efficiency evaluated. The influence of temperature on enzyme activity, as well as the thermal stability and reusability of devices, were also investigated.
Reactive and Functional Polymers 01/2014; · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract In this study, pH-responsive hydrogels, synthesized by the coupling reaction of polyacrylic acid and catechin, are proposed as carriers of oxidable drugs toward the GI tract. The presence of polyphenolic moieties in the network gives the polymers properties suitable for the release of unstable drugs in oxidative conditions. The characterization of the hydrogels is obtained by means of morphological and physico-chemical analyses, antioxidant assays and evaluation of the swelling behavior in media simulating the gastric (pH 1.0) and the intestinal (pH 7.4) tracts. The hydrogels are tested as pH-responsive carriers in in vitro release studies of folic acid and thiamine, two model drugs easily degraded by oxidative conditions simulated by UV irradiation and t-butyl hydroperoxide treatment, respectively. Results show that catechin-based carriers are able to control the release of drugs at different pH values, giving a remarkable improvement in the stability of the therapeutics.
Pharmaceutical Development and Technology 12/2013; · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: The aim of the present study was to prepare a hydrogel, based on ellagic acid and glycine, embedded with folic acid, as a subcutaneous implant for the treatment of breast cancer. The function of folic acid is to selectively and actively target tumor cells which are well-known to overexpress folic acid receptors on their surface.
A pro-drug based on L-glycine and ellagic acid, was functionalized with a polymerizable group and loaded with folic acid to make it more natural, non-toxic, compatible and specific for the site of action. Cytotoxicity against MCF-7 cells was also evaluated. Release studies of folic acid were conducted on aliquots of hydrogel at different pH (6.2 and 7.4) and time-points (1, 6, 12 and 24 h) using a shaking water bath at 37°C (body temperature).
Our results show that folic acid release by the hydrogel is characterized by a slow kinetic release, especially at pH 6.2. Moreover, it was evidenced that the exposure of human breast cancer cells to ellagic acid-based hydrogel containing folic acid significantly reduced cell viability.
Anticancer research 11/2013; 33(11):4847-54. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Niosomal vesicular systems containing resveratrol, alpha-tocopherol and curcumin as single agents and in combination, were designed with the aim to develop novel cosmeceutical formulations. The effects of antioxidants co-encapsulation on the physico-chemical properties of the carriers, their antioxidant properties and in vitro percutaneous permeation profiles were evaluated. Results showed that the co-encapsulation of resveratrol/curcumin and alpha-tocopherol/curcumin affected the physico-chemical properties of niosomes and the entrapment efficiencies values, respect to the formulations containing the single antioxidant. The antioxidants in vitro percutaneous permeations appeared to be controlled and improved respect to the corresponding free solutions used as control. Moreover the antioxidants combinations resulted in a promoted ability to reduce free radicals, due to a synergic antioxidant action.
[Show abstract][Hide abstract] ABSTRACT: Recently niosomes have been used as nutraceutical vehicles of functional components, useful in the prevention of many diseases caused by oxidative stress, with the aim to control their delivery into the body and to increase the nutritional quality of food dairy products with which these products can be enriched. We decided to develop novel niosomal formulations containing nutritional supplements such as gallic acid, ascorbic acid, curcumin and quercetin as single agents and in combination, to evaluate the effect of the active molecules co-encapsulation on the physico-chemical properties of the carriers, on their antioxidant properties and capability of releasing the encapsulated materials. Results suggest that the co-encapsulations of gallic acid/curcumin and ascorbic acid/quercetin mix influence their physico-chemical properties and their entrapment efficiencies respect to the formulations containing the single antioxidant; also the antioxidants releases appeared to improve and their combinations resulted in a promoted ability of reducing free radicals, due to a synergic antioxidant action.
[Show abstract][Hide abstract] ABSTRACT: Different fluoroquinolon-type antibiotics were conjugated to gelatin with the aim to synthesize biomacromolecules with antimicrobial properties. The covalent linkage of the antibiotic was performed by a radical process involving the residues in the side chains of gelatin able to undergo oxidative modifications. The conjugation of antibiotic moieties onto the protein structure was confirmed by FT-IR, UV-Vis, fluorescence, and calorimetric analyses. Biocompatibility tests were performed on human bone marrow mesenchymal stromal cells and the antibacterial properties of bioactive polymers were investigated by appropriate tests against Klebsiella pneumoniae and Escherichia coli. With regard to the tests conducted in the presence of E. coli, a minimum inhibitory concentration (MIC) ranging from 0.05 to 0.40 μg mL(-1) was recorded, while in the presence of K. pneumoniae this concentration varies from 0.10 to 1.60 μg mL(-1). In all the conjugates, the drug moieties retain their biological activity and the MIC values are lower than the resistance parameters of fluoroquinolon-type antibiotics versus Enterobacteriacae. The collected data suggest a broad range of applications, from biomedical to pharmaceutical and food science for all conjugates.
Journal of Materials Science Materials in Medicine 10/2013; · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray‐drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro. Methods
Microparticles were obtained by spray drying, and their morphology, size, zeta potential, thermotropic behaviour and nebulisation ability were evaluated. Key findings Microparticles were positively charged with a mean size of 4.88 ± 0.3 μm. Microspheres were able to incorporate both RFP and ISN: encapsulation efficiency was 51 ± 6% and 22 ± 1%, respectively. X‐ray diffraction study showed a new extensive and flattened diffraction peak providing evidence that the drugs were dispersed into the microparticles. Differential scanning calorimetry analysis confirmed effective interactions between gelatin and drug molecules by the presence of new transition peaks. Fifty‐nine per cent of used microparticles were aerosolised. In‐vitro toxicity studies on A549 alveolar basal epithelial cells showed that microparticles decreased cytotoxicity in comparison with the RFP solution. Laser scanning confocal microscopy observation confirmed that fluorescent probes delivered by microparticles are efficiently internalised in A549 cells. Conclusions Overall, microparticles based on gelatin covalently bound to ISN and containing RFP showed a promising behaviour for pulmonary drug delivery.
[Show abstract][Hide abstract] ABSTRACT: An efficient tumor targeted-niosomal delivery system for the vehiculation of doxorubicin hydrochloride as an anticancer agent was designed. Niosomes were prepared from a mixture of an opportunely modified Pluronic L64 surfactant and cholesterol as membrane additive and characterized in terms of dimension, distribution size, morphology and doxorubicin entrapment efficiency. After the preparation, Transferrin was conjugated to niosomes in order to produce Tf-niosomes and citotoxicity of the final formulation was studied. The specific uptake of Tf-niosomes into cells was evaluated incubating MCF-7 and MDA-MB-231 cells with fluorescently Rhodamine loaded Tf-niosomes for various times and concentration intervals and further investigated by fluorescence microscopy. Results showed that doxorubicin can be easily encapsulated into niosomes, that are regular and spherical in shape. Moreover, Tf-conjugate niosomes demonstrated far greater extent of cellular uptake to MCF-7 and MDA-MB-231 cells, suggesting that they were mainly taken up by Tf-R mediated endocytosis. Doxorubicin-loaded niosomes anticancer activity was also achieved against MCF-7 and MDA-MB-231 tumoral cell lines and a significant reduction of viability in a dose- and time-related manner was observed. Finally our formulation could be potentially useful as target doxorubicin delivery system in anticancer therapy.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES : In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray-drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro.
Microparticles were obtained by spray drying, and their morphology, size, zeta potential, thermotropic behaviour and nebulisation ability were evaluated. KEY FINDINGS : Microparticles were positively charged with a mean size of 4.88 ± 0.3 μm. Microspheres were able to incorporate both RFP and ISN: encapsulation efficiency was 51 ± 6% and 22 ± 1%, respectively. X-ray diffraction study showed a new extensive and flattened diffraction peak providing evidence that the drugs were dispersed into the microparticles. Differential scanning calorimetry analysis confirmed effective interactions between gelatin and drug molecules by the presence of new transition peaks. Fifty-nine per cent of used microparticles were aerosolised. In-vitro toxicity studies on A549 alveolar basal epithelial cells showed that microparticles decreased cytotoxicity in comparison with the RFP solution. Laser scanning confocal microscopy observation confirmed that fluorescent probes delivered by microparticles are efficiently internalised in A549 cells. CONCLUSIONS : Overall, microparticles based on gelatin covalently bound to ISN and containing RFP showed a promising behaviour for pulmonary drug delivery.
The Journal of pharmacy and pharmacology. 09/2013; 65(9):1302-11.
[Show abstract][Hide abstract] ABSTRACT: In this study, stearic acid- and stearyl ferulate-based solid lipid nanoparticles containing trans-ferulic acid (SLN-FA and SLN-SF-FA, respectively), were prepared and characterized for loading efficiency, size and shape. In addition, by using rat brain microsomes, we evaluated in vitro the antioxidant activity of these formulations against three well known initiators of lipid peroxidation, such as AAPH, NADPH/ADP-Fe(3+) and SIN-1 which in turn generate the peroxyl and perferryl radicals as well as peroxynitrite, respectively. Commercially available FA and its ethyl ester (FAEE) were used as comparators. Both SLN-FA and SLN-SF-FA dose-dependently reduced lipid peroxidation induced by the three oxidants. Interestingly, SLN-SF-FA displayed greater efficacy (EC50) and potency (maximal activity) against AAPH- and NADPH/ADP-Fe(3+)-induced lipid peroxidation. Our results support the idea that this new formulations could facilitate the uptake of FA by the cells because of their lipophilic structure, thus increasing FA bioavailability. Furthermore, stearyl ferulate-based nanoparticles could prevent the degradation of FA entrapped on their structure, making FA almost entirely available to explicate its antioxidant power once released.