Delivery Of Water-soluble Drugs Research Articles

A Comprehensive Review of Self-Nanoemulsifying Systems in the Delivery of Herbal Drugs.

Self-nanoemulsifying drug delivery systems (SNEDDS) are an isotropic mixture of oils, co-surfactants, and surfactants and can form fine O/W Nanoemulsions in aqueous media. These components are advantageous in terms of improved solubility and bioavailability. Limited permeability, solubility, and bioavailability remain a significant challenge in developing herbal drugs. This review explores the potential of self-nanoemulsifying drug delivery systems (SNEDDS) as a promising strategy to overcome this problem. The SNEDDS is considered a novel technique for the delivery of low water-soluble drugs. It can bypass the first-pass metabolism, resulting in steady and sustained drug levels in the systemic circulation. The present article provides a comprehensive overview of the SNEDDS formulation of herbal drugs. It includes their composition, characterization, in vitro and in vivo studies conducted in various disease conditions, and pharmacokinetic studies.

Fast-dissolving electroactive drug delivery systems: Gelatin/Poly(sulphonic acid diphenyl aniline) electrospun nanofibers

In this study, bovine gelatin (Gel)/poly(sulfonic acid diphenyl aniline) (PSDA) electrospun nanofibers were produced with PSDA, a water-soluble polyzwitterion ion thanks to sulfonyl groups, and Gel, a biocompatible and biodegradable natural polymer. These electrospun nanofibers are both electroactive and water-soluble. Cyclic voltammetry technique was used to examine the electroactivity of these nanofibers, which were used as unsupported direct working electrodes. According to the cyclic voltammograms, when the PSDA ratio in Gel/PSDA nanofibers was increased from 5% to 20%, the highest oxidation current value increased from 3.29 nA to 14.33 nA. These water-soluble electroactive nanofibers were loaded with methimazole as a model drug, and their cumulative release occurred within a few seconds. FTIR, UV–Vis spectroscopy, TG/DTA, XRD, DMA, SEM and EDS were used for characterizations.These water-based fast-dissolving electroactive Gel/PSDA electrospun nanofibers, presented for the first time in this study, were produced safely, quickly and at relatively low cost. In addition to being used as a new water-soluble drug delivery system, these nanofibers can also be used in other bioapplications such as biosensors and tissue engineering because they are electroactive.

NMR Study of Water-Soluble Carotenoid Crocin: Formation of Mixed Micelles, Interaction with Lipid Membrane and Antioxidant Activity.

Crocin is a unique water-soluble carotenoid found in crocus and gardenia flowers. Crocin has been shown to have a variety of pharmacological activities, such as antioxidant, anti-cancer, memory improvement, antidepressant, anti-ischemia, blood pressure lowering and aphrodisiac, gene protection and detoxification activities. Due to their amphiphilicity, crocin molecules form concentration-dependent self-associates (micelles) in a water solution. In the present study, using various NMR techniques (T2 relaxation and selective gradient NOESY), we have demonstrated that crocin forms mixed micelles with water-soluble drug delivery system glycyrrhizin and linoleic acid molecules. Note, that the spin-spin T2 relaxation time and NOESY spectroscopy are very sensitive to intermolecular interactions and molecular diffusion mobility. The second purpose of this work was the elucidation of the interaction of crocin with a model lipid membrane using NMR techniques and a molecular dynamics simulation and its effects on lipid oxidation. It was shown that the crocin molecule is located near the surface of the lipid bilayer and effectively protects lipids from oxidation by peroxyl radicals. The role of glycyrrhizin and vitamin C in metal-induced lipid oxidation was also elucidated. The results of this study may be useful for expanding the field of application of crocin in medicine and in the food industry.

Nanocapsules novel drug delivery system: A review

Nanocapsules have been various sub micrometer poorly water–soluble drug delivery systems comprised of the oil–based predicated or even a solubilized fundamental enveloped besides synthetic polymer cell wall. Nanocapsules have indeed been vesicular processes where the narcotic seems to be restricted to the pore largely made up of pore water fundamental encapsulated by the polymeric. Nanocapsules are used as only two types after all synthetic polymers. Natural polymers a Synthetic polymers. Nanocapsules have indeed been prepared by different methods some of these have been the Nanoprecipitation method, Emulsion diffusion method, Double emulsification method, Emulsion coacervation method, Polymer coating method, and Layer –by-Layer. Different characterization along with evaluation methods have been performed full nanocapsules dispersed polyethylene nanocapsules is used even though sub-micron narcotic wants to pick up to get a slow release together with efficient drug looking to attack. Microparticles, residing all through relatively small size, range once 10 nanometers to 1000 nanometers they include a fluid/ strong core wherein the drug has been placed into a pore, which would be enveloped by a special and distinct thermoplastic polymer constituted after all synthetic as well as bioplastic they’ve attracted super great awareness, so because barrier methods coting, which really have been usually pyrophoric and easily metabolizable along with slow this very same discharges chemical ingredients.

Formulation and evaluation of topical piroxicam microemulgel for arthritis

Background: Piroxicam is an anti-inflammatory, analgesic, and antipyretic drug. Piroxicam is widely used in the management of chronic pain. The objective of this work was to develop and analyze topical Piroxicam microemulgel to improve drug solubility, enhance permeation, reduce GIT side effects reduce the frequency of the drug. Method: The Piroxicam microemulgel was prepared by drawing the pseudo ternary phase picture and water titration procedure. Formulation was prepared by using isopropyl myristate as an oil, Tween 80 as an surfactant, n-butanol as Co-surfactant and water. It was converted to gel by using 1% Carbopol 940 and few drops of ethanolamine. The prepared formulation was characterized for thermodynamic stability, pH, droplet size, viscosity, FTIR,DSC, electrical conductivity, dye solubility drug content, and in-vitro release using a Franz diffusion cell. Result: Microemulgel formulation was thermodynamically stable on visual inspection after being treated with a freeze-thaw cycle and centrifugation. pH of formulation was 6.5. The mean droplet size for ME gel was 100±0.472nm. The viscosity of the microemulgel was 90.4±0.01 cps which showed Newtonian flow. FTIR and DSC studies showed that microemulgel was compatible with its excipients. Electrical conductivity and dye solubility testing confirmed that the microemulgel was O/W. Piroxicam microemulsion gel showed 89.89% drug content and the release rate of piroxicam was 98±8.63% after 48h. It followed the Korsmeyer Pappas model which means it was a hydrogel-based system. Conclusion: Microemulsion gel formulation obtained remarkably inflated skin retention for piroxicam over the piroxicam gel. It might act as a promising vehicle for the topical delivery of poor water-soluble drugs.

Formulation and evaluation of topical piroxicam microemulgel for arthritis

Background: Piroxicam is an anti-inflammatory, analgesic, and antipyretic drug. Piroxicam is widely used in the management of chronic pain. The objective of this work was to develop and analyze topical Piroxicam microemulgel to improve drug solubility, enhance permeation, reduce GIT side effects reduce the frequency of the drug. Method: The Piroxicam microemulgel was prepared by drawing the pseudo ternary phase picture and water titration procedure. Formulation was prepared by using isopropyl myristate as an oil, Tween 80 as an surfactant, n-butanol as Co-surfactant and water. It was converted to gel by using 1% Carbopol 940 and few drops of ethanolamine. The prepared formulation was characterized for thermodynamic stability, pH, droplet size, viscosity, FTIR,DSC, electrical conductivity, dye solubility drug content, and in-vitro release using a Franz diffusion cell. Result: Microemulgel formulation was thermodynamically stable on visual inspection after being treated with a freeze-thaw cycle and centrifugation. pH of formulation was 6.5. The mean droplet size for ME gel was 100±0.472nm. The viscosity of the microemulgel was 90.4±0.01 cps which showed Newtonian flow. FTIR and DSC studies showed that microemulgel was compatible with its excipients. Electrical conductivity and dye solubility testing confirmed that the microemulgel was O/W. Piroxicam microemulsion gel showed 89.89% drug content and the release rate of piroxicam was 98±8.63% after 48h. It followed the Korsmeyer Pappas model which means it was a hydrogel-based system. Conclusion: Microemulsion gel formulation obtained remarkably inflated skin retention for piroxicam over the piroxicam gel. It might act as a promising vehicle for the topical delivery of poor water-soluble drugs.

GPP-TSAIII nanocomposite hydrogel-based photothermal ablation facilitates melanoma therapy

ABSTRACT Background Photothermal therapy (PTT) is a promising cancer treatment, but its application is limited by low photoconversion efficiency. In this study, we aimed to develop a novel graphene oxide (GO)-based nanocomposite hydrogel to improve the bioavailability of timosaponin AIII (TSAIII) while maximizing PTT efficacy and enhancing the antitumor effect. Methods GO was modified via physical cross-linking with polyvinyl alcohol. The pore structure of the gel was adjusted by repeated freeze-thawing and the addition of polyethylene glycol 2000 to obtain a nanocomposite hydrogel (GPP). The GPP loaded with TSAIII constituted a GPP-TSAIII drug delivery system, and its efficacy was evaluated by in vitro cytotoxicity, apoptosis, migration, and uptake analyses, and in vivo antitumor studies. Results The encapsulation rate of GPP-TSAIII was 66.36 ± 3.97%, with slower in vitro release and higher tumor cell uptake (6.4-fold) compared to TSAIII. GPP-TSAIII in combination with PTT showed better bioavailability and antitumor effects in vivo than did TSAIII, with a 1.9-fold higher tumor suppression rate than the TSAIII group. Conclusions GPP is a potential vehicle for delivery of TSAIII-like poor water-soluble anticancer drugs. The innovative PTT co-delivery system may serve as a safe and effective melanoma treatment platform for further anticancer translational purposes.

Thermoresponsive Water-in-Oil-in-Water Pickering Double Emulsions Stabilized with Biodegradable and Semicrystalline Poly(ethylene glycol)-b-poly(ε-caprolactone-co-δ-valerolactone) Diblock Copolymer Micelles for Controlled Release.

Water-in-oil-in-water (W/O/W) Pickering double emulsions are promising materials for the construction of carriers for water-soluble and oil-soluble molecules or drug delivery systems if the contradictive trade-off between their extreme stability and controlled release properties can be resolved. In this study, biodegradable and biocompatible poly(ethylene glycol)-b-poly(ε-caprolactone-co-δ-valerolactone) (PEG-b-PCVL) diblock copolymers with predesigned hydrophilic to hydrophobic block length ratios and nearly identical ε-caprolactone/δ-valerolactone molar ratio (8/2), were synthesized by ring-opening copolymerization. Then, they self-assembled to create semicrystalline micelles. The melting points of PEG-b-PCVL copolymers and their lyophilized micelles were within a physiological range of temperatures, as determined by differential scanning calorimetry. Water contact angle measurements provided evidence that the surface wettability of PEG-b-PCVL micelles could be tuned by the PCVL block mass fractions or temperature stimulus. Such PEG-b-PCVL micelles were employed as a single particulate stabilizer to develop Pickering double emulsions through a one-step emulsification technique. W/O/W Pickering double emulsions could be generated using relatively hydrophobic PEG-b-PCVL micelles with high mass fractions (exceeding about 89%) of PCVL blocks, and they displayed excellent long-term physical stabilities at room temperature. However, the Pickering double emulsions underwent a rapid microstructural transition into simple oil-in-water Pickering emulsions instead of complete demulsification at elevated temperature (37 °C), which was attributed to the hydrophilicity of micelles enhanced when the core-forming PCVL melted realized by temperature stimulus. Consequently, such W/O/W Pickering double emulsions stabilized solely with semicrystalline PEG-b-PCVL micelles exhibit thermal responsiveness, enabling them to release vitamin B12 encapsulated within the internal aqueous phase rapidly.

Influence of Process Variables on Budesonide Nanoparticles Using Factorial Design

Aims: Nanoparticles are the colloidal carrier systems for delivery of poorly soluble drugs. Budesonide. (BUD) a corticosteroid practically insoluble in water is used in asthma treatment. The aim of the present research work was to develop and evaluate BUD nanoparticles.
 Methodology: The prepared formulation was analyzed for % encapsulation efficiency, particle size analysis, zeta potential, polydispersity index (PDI), scanning electron microscopy and transmission electron microscopy. Poloxamer-188 was found in stabilizing BUD nanoparticles.
 Results: The observed % encapsulation efficiency of the optimized batch was (82.95) %, particle size was 271.8 nm with PDI 0.456. Solvent injection method was successfully implemented to developed BUD nanoparticles poloxamer-188. Sonication time and amplitude played an important role in governing the particle size.
 Conclusion: It can be inferred from the study that nanoparticles are a potential drug delivery method for poorly water-soluble drug delivery which can not only get impacted by formulation variables but also by process variables.

Brain-targeting delivery of MMB4 DMS using carrier-free nanomedicine CRT-MMB4@MDZ

Brain-targeting delivery of 1,1′-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) is limited by its hydrophilic property and chemical instability. In order to solve this problem, herein, we develop a facile protocol through combining antisolvent precipitation and emulsion-solvent evaporation method to synthesize midazolam (MDZ) coated MMB4 DMS (MMB4@MDZ) nanoparticles. The as-prepared MMB4@MDZ had a MMB4 DMS nanocrystal (MMB4-NC) core and a MDZ shell. The MDZ shell prevented the MMB4-NC core from contacting the aqueous environment, and thus, guaranteed the chemical stability of MMB4 DMS. Most charmingly, the iron mimic cyclic peptide CRTIGPSVC (CRT) was modified on MMB4@MDZ surfaces to produce CRT-MMB4@MDZ which was endowed with ability to absorb transferrin (Tf)-abundant corona. Taking advantages of the Tf-abundant corona, CRT-MMB4@MDZ achieved transferrin receptor (TfR)-mediated brain-targeting delivery. With the fascinating chemical stability and brain-targeting delivery effect, CRT-MMB4@MDZ showed great clinical transform prospect as a brand-new nanomedicine. Of particular importance, this work promised not only a core–shell carrier-free nanomedicine platform for effective delivery of unstable water-soluble drug, but also a protein corona-manipulating strategy for targeting delivery.

Optimization, physicochemical characterization, and antimicrobial activity of a novel simvastatin nano-niosomal gel against E. coli and S. aureus

Niosomes, as a kind of drug delivery system, is widely used for the topical delivery of lipophilic drugs. Optimization of niosomes plays an essential role in enhancing their therapeutic efficiencies. This study aims to prepare an optimized niosomal formulation of simvastatin (nSIM), a lipophilic member of statins, through the experiment (Response Surface methodology). Optimized niosomes were characterized in size, polydispersity index (PDI), entrapment efficiency (EE), stability, releasing pattern, and antimicrobial activity. The different molar ratio of surfactant and cholesterol were applied to prepare various formulation of simvastatin loaded niosome. Mean particle size and size distribution were analyzed by dynamic light scattering. Antibacterial activity was determined by MIC and MBC tests against Staphylococcus aureus and Escherichia coli. The release rate of simvastatin from noisome nanoparticles was studied by the Franz diffusion cell method. The release pattern was studied through zero order, first order, Higuchi, Korsmeyer-Peppas, and Hixson-Crowell kinetics models. Optimized niosomes were obtained by span 80, drug to cholesterol ratio of 0.4 with 7 min sonication time. Mean particle size, PDI, zeta potential, and entrapment efficiency (EE%) of optimized nSIM were obtained about 168 nm, 0.34, -32.40, and 96 %, respectively. The niosomes significantly decreased the drug's releasing rate and enhanced antibacterial activity against S. aureus and E. Coli. It was found that the release pattern of drug followed the Higuchi kinetic model which means drug release is by diffusion. Overall, our findings indicated that the prepared simvastatin loaded niosomes showed good stability and biological properties than free drug. Our study suggests that niosomal formulation could be considered as a promising strategy for the delivery of poor water-soluble drugs that enhance antibacterial activity.

Niosomal delivery of simvastatin to MDA-MB-231 cancer cells

Objective The objective of this study was to use nano-niosomal formulations to deliver simvastatin as a poor-water soluble drug into breast cancer cells. Significance Our study focused on the problem associated with poor water-soluble drugs which have significant biological activity in vivo. Methods Different niosomal formulations of simvastatin were prepared and characterized in terms of morphology, size, encapsulation efficiency (EE), and release kinetic. Antiproliferative activity and the mechanism were assessed by quantitative real-time PCR and flow cytometry. Moreover, confocal microscopy was employed to analyze the cell uptake of simvastatin loaded niosomes to the cancerous cells. Results Size, polydispersity index (PDI), and EE of the best formulation were obtained as 164.8 nm, 0.232, and 97%, respectively. The formulated simvastatin had a spherical shape and showed a slow release profile of the drug after 72 h. Stability data elucidated an increase in mean diameter and PDI which was lower for 4 °C than 25 °C. Confocal microscopy showed the localization of drug loaded niosomes in the cancer cells. The MTT assay revealed both free drug and drug loaded niosomes exhibited a dose-dependent cytotoxicity against breast cancer cells (MDA-MB-231 cells). Flow cytometry and qPCR analysis revealed drug loaded niosomes exert their cytotoxicity on cancerous cells via regulation of apoptotic and anti-apoptotic genes. Conclusion The prepared niosomal simvastatin showed good physicochemical and biological properties than free drug. Our study suggests that niosomal delivery could be considered as a promising strategy for the delivery of poor water-soluble drugs to cancer cells.

Microemulsions based on polyglycerol polyricinoleate as drug delivery systems

The aim of the work is to develop composition of reverse microemulsion stabilized by the surfactant from a number of polyglycerol polyricinoleates for encapsulating water-soluble biologically active substance (BAS) and studying the kinetics of its release into the medium simulating the medium of the small intestine. Materials and methods. Possible stable (equilibrium) phases of the reverse microemulsion in the pseudoternary system water–PG-3-PR/Tween 80–paraffin oil were determined by titration of surfactant/co-surfactant mixtures–oil in water with hydrophilic-lipophilic balance (HLB) values of the surfactant mixture ranging from 4.0 to 7.0. Stability of a number of compositions during storage at 20 °C for 6 months was studied. Based on the obtained data, a composition was selected for encapsulating methylene blue (MS) dye as a model of a water-soluble biologically active substance. Microemulsion was obtained by mixing paraffin oil and surfactants with selected mass ratio followed by the addition of an aqueous phase. Reverse microemulsion morphology was evaluated with transmission electron microscopy (TEM). To evaluate the in vitro drug release rate, aliquots of an aqueous dye solution (control sample) and MB-containing microemulsions were placed in dialysis bags and immersed in 0.01 M phosphate-buffered saline (PBS) (pH 7.4) in a thermostatic shaking incubator at 180 rpm and 37 °C. Aliquots of the release medium were selected at predetermined time intervals and the concentration of MB dye was determined using a UV spectrophotometer at 660 nm. Results. Composition containing 13.5 wt% paraffin oil, 76.5 wt% mixture of PG3-PR/Tween 80 (HLB 5.5) and 10 wt% water was chosen to encapsulate the biologically active agents. Number average droplet diameter in the dispersed phase of the obtained microemulsion was 55 nm. Dye-loaded microemulsion sample showed a prolonged release of biologically active substances within 48 hours of the experiment (15.2%) and low initial release rate. Conclusion. Possible stable phases of reverse microemulsion in the pseudoternary system water–PG-3-PR/Twin 80–paraffin oil were determined in the course of the work and optimal microemulsion composition for encapsulating medicinal substances was found. It was shown that the resulting microemulsion system provides a sustained release of methylene blue as a model of a water-soluble biologically active substance in a medium simulating medium of the small intestine. The obtained data allow to consider this composition as a potential nanoscale system for the sustained delivery of water-soluble drugs.

Double-nano silica xerogel contributes to establish nifedipine delivery system with superior delivery effect

Abstract To further explore the wonder of nano technology in drug delivery system, the combination of micelles and mesoporous silica was conducted for delivering poorly water soluble nifedipine (NFP). Double-nano silica xerogel (DN-SX) with both micelles and nanopores was prepared and silica xerogel with only nanopores (SN-SX) was made for comparison. Characteristics of DN-SX and SN-SX, including morphology, porous structure and crystalline state were investigated and pharmaceutical performances of drug loaded carriers were studied. The micelles in DN-SX contributed to achieve larger mesopores and enhanced NFP dissolution better than SN-SX. How responses of drug release amount and reduced drug release amount reacted as changing each influencing factor was elucidated by Box–Behnken experimental design. With the DN-SX obtained by optimization, in vivo pharmacokinetic study result demonstrated that the relative bioavailability of NFP loaded DN-SX and NFP loaded SN-SX were 216.84% and 161.14%, respectively. Therefore, the optimized DN-SX with double-nano structure was of great value for designing poorly water soluble drug delivery system.

Development and evaluation of a pH-responsive and water-soluble drug delivery system based on smart polymer coating of graphene nanosheets: an in silico study.

The objective of this study is to develop a controlled and water-soluble delivery system for doxorubicin (DOX) based on the coating of graphene (G) with a smart polymer. A combination of polyethyleneimine (PEI) and G–DOX is investigated by performing density functional theory (DFT) calculations and molecular dynamics (MD) simulations. Several parameters have been employed to evaluate the effect of PEI on the adsorption and release mechanisms of DOX. The obtained results indicated that the binding energy of the drug molecule on G in the presence of PEI is enhanced by about 20% under neutral conditions, whereas the drug absorption becomes weaker in an acidic environment so that DOX could be separated from the carrier surface using near-infrared radiation (NIR). Based on the atom in molecule (AIM) theory, two hydrogen bonds with strengths of about −12.59 and −39.99 kJ mol−1 have been established. Furthermore, evaluating the dynamic behavior of the designed systems in water solution shows that the polymer in physiological pH rapidly adsorbed on the drug–carrier complex. However, at acidic pH, it is quickly desorbed from the carrier surface and the G–DOX complex can be exposed to cancer cells. The obtained results of the present research may be used in future experimental work to design smart DDSs.

Development of Dried Emulsion/Mannitol Composite Microparticles through a Unique Spray Nozzle for Efficient Delivery of Hydrophilic Anti-tuberculosis Drug against Alveolar Macrophages.

As alveolar macrophages are attractive targets for the treatment of tuberculosis, effective methods for delivery to alveolar macrophages are under development. We investigated a pulmonary formulation for the efficient delivery of high water-soluble drugs at high concentration targeting alveolar macrophages. In this study, a surfactant-coated high water-soluble drug complex (SDC, a hydrophobic dried emulsion), which can preferably target alveolar macrophages and be expected to deliver drug at a high concentration, was prepared in the first process. OCT313, a high water-soluble sugar derivative with anti-tuberculosis activity was used. Then, a unique two-solution, mixing-type nozzle was used to prepare the SDC nanoparticles in mannitol (MAN) microparticles (SDC/MAN microparticles) because it was difficult to disperse the SDC nanoparticles in aqueous solution. The single micron size of OCT313-SDC/MAN microparticles contained OCT313-SDC nanoparticles (mean particle size of OCT313-SDC nanoparticles, 277.9 nm; drug contents, 1.31 ± 0.041 wt%). We found that the treatment of SDC/MAN microparticles exhibited significantly higher drug accumulation in macrophage cells (Raw264.7 cells, 7.5-fold, at 4 h after treatment) in vitro and in alveolar macrophages in rats (9.1-fold, at 4 h after treatment) in vivo than that of drug alone. These results suggest that the SDC/MAN microparticle formulation prepared by spray drying through a two-solution mixing-type nozzle provides efficient delivery of a water-soluble drug targeting alveolar macrophages and may be useful for tuberculosis treatment.

Development and characterization of Solid-SNEDDS formulation of DHA using hydrophilic carrier with improved shelf life, oxidative stability and therapeutic activity

Docosahexanoic acid (DHA) is an essential element for proper development of brain and treatment of cognitive disorders. Oily nature, poor water dispersibility, intestinal permeability, organoleptic characteristic of microalgae oil (DHA oil) limits oral delivery and therapeutic performance. An effort has been made to prepare a novel water soluble Solid Self Nano-Emulsifying Drug Delivery System (S-SNEDDS) of DHA oil having improved physical & oxidative stability, bioavailability and therapeutics using spray drying technology. Optimized S-SNEDDS showed small and spherical shape particles with good water dispersibility, oxidative stability and flow properties, ideal for developing solid dosage forms. DSC and XRD studies depicted amorphous nature of S-SNEDDS with complete dispersion of DHA oil in carrier matrix. Cytotoxicity assay showed nontoxic nature of the developed formulation with no change in Transepithelial electrical resistance (TEER) and paracellular permeability of Caco-2 cells. Ex-vivo studies depicted 5 & 2 fold increase in DHA absorption in intestinal permeability and Caco- 2 uptake studies. In vivo pathophysiological role of DHA in preventing cognitive decline was evaluated with Melamine induced cognitive impairment and treatment with S-SNEDDS was found to augment the role of DHA. Thus, S-SNEDDS improved physicochemical properties and is cost effective pharmaceutical approach to increase clinical uses of DHA.

Tunable vegetable oil/silica hybrid microparticles for poorly water-soluble drug delivery.

To encapsulate and deliver poorly water-soluble drugs, castor oil/silica hybrid microparticles (HMP)s were synthesized. Green chemistries were used to silylate the oil and further cross-link it into solid microparticles by sol-gel reaction. Silylated castor oils (ICO)s at various silylation ratios were prepared and allowed the solubilization of ibuprofen at several concentrations up to 16 wt%. The HMPs were formulated by ThermoStabilized Emulsion (TSE) process which permits to "freeze" the oil-in-water emulsion while the sol-gel reaction occurs. The hybrid mineral/organic composition and the morphology (spherical shape and micrometric size) of these HMPs were determined by complementary technics (SEM, TGA, EDX, 29Si NMR and FTIR spectroscopies). The HMPs reached a good ibuprofen loading efficiency regardless to the formulation used while the release kinetics in simulated oral administration exhibited a tunable release during 3 h according to the silylation ratio. The ibuprofen rate also influenced its own amorphous or crystalline character within the HMPs. For subcutaneous conditions, ibuprofen release took place over 15 days. Finally, biodegradability assays in simulated digestion medium suggested a surface-limited hydrolysis of the particles and cytocompatibility studies on NIH-3T3 and Caco-2 cells demonstrated an excellent cellular viability.

Citric acid crosslinked carboxymethylcellulose-polyvinyl alcohol hydrogel films for extended release of water soluble basic drugs

The aim of present work was to develop carboxymethylcellulose (CMC)-polyvinyl alcohol (PVA) hydrogel films for extended delivery of water soluble basic drug, using citric acid (CA) as a cheap and non-toxic crosslinking agent. Gentamicin sulfate (GTM) was used as a model drug. The hydrogel films were evaluated for carboxyl content, tensile strength, swellability, drug loading and release, hemocompatibility and characterized by 13C-CP-MAS NMR, ATR-FTIR and thermal analysis (TGA and DSC). The instrumental analysis helped to confirm the formation of ester crosslinks. CMC-PVA hydrogel films exhibited greater carboxyl content, tensile strength and swellability than the pure CMC hydrogel films. The GTM loading increased with an increase in the amount of PVA in the hydrogel films. The CMC-PVA hydrogel films showed propensity to extend the release of GTM above 24 h. Hemolysis assay revealed the hemocompatible nature of the hydrogel films. Altogether, the CMC-PVA hydrogel films can be envisioned as promising biomaterial for the delivery of water soluble basic drugs.

Semi-solid prodrug nanoparticles for long-acting delivery of water-soluble antiretroviral drugs within combination HIV therapies

The increasing global prevalence of human immunodeficiency virus (HIV) is estimated at 36.7 million people currently infected. Lifelong antiretroviral (ARV) drug combination dosing allows management as a chronic condition by suppressing circulating viral load to allow for a near-normal life; however, the daily burden of oral administration may lead to non-adherence and drug resistance development. Long-acting (LA) depot injections of nanomilled poorly water-soluble ARVs have shown highly promising clinical results with drug exposure largely maintained over months after a single injection. ARV oral combinations rely on water-soluble backbone drugs which are not compatible with nanomilling. Here, we evaluate a unique prodrug/nanoparticle formation strategy to facilitate semi-solid prodrug nanoparticles (SSPNs) of the highly water-soluble nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine (FTC), and injectable aqueous nanodispersions; in vitro to in vivo extrapolation (IVIVE) modelling predicts sustained prodrug release, with activation in relevant biological environments, representing a first step towards complete injectable LA regimens containing NRTIs.