Investigation on release of highly water soluble drug from matrix-coated pellets prepared by extrusion–spheronization technique

The objective was to formulate itopride HCl (ITP) extended release matrix-coated pellets by extrusion–spheronization and to investigate the influence of concentration and viscosity grade of different polymers on release of a highly water soluble drug. The matrix pellet formulations consisted of polymers (10–30%) like hydroxypropyl methylcellulose (HPMC K4M, K15M, and K100M), ethyl cellulose (EC-7 cps), microcrystalline cellulose (10–30%) and a fixed quantity of lactose (10%). The initial fast drug release from the matrix pellets was effectively controlled by coating with 5% ethyl cellulose (10 cps) dispersion. The dissolution studies of coated formulations were carried out at different pH, and data were analyzed for drug release kinetics. Scanning electron microscope was used to examine the surface morphology and cross section of pellets. Kinetics of all coated formulations were best explained by Higuchi model (R ² = 0.94–0.99). However, HPMC matrix-coated pellets (F1, F4 and F7) also followed Baker and Lonsdale model (R ² = 0.96–0.99), whereas, EC matrix-coated pellets (F10) followed zero-order kinetics (R ² = 0.99). Release mechanism of all coated formulations was non-fickian. Both uncoated and coated pellets were found to be spherical. Fourier transform infrared spectroscopy was conducted on the coated formulations and no drug–excipients interaction was found.     

Development of transdermal drug‐delivery films with castor‐oil‐based polyurethanes

Two different types of polyurethanes (PUs) were prepared with castor oil, ethylene glycol, isophorene diisocyanate and castor oil, and isophoren diisocyanate and poly‐(ethylene glycol) (400 or 600). PU films were prepared and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and gel permeation chromatography. We prepared transdermal patches by loading different amounts of drug, plasticizer, and penetration enhancer. In vitro drug permeability through the castor‐oil‐based aliphatic PU patches was examined with a Keshary–Chien diffusion cell. The effect of castor oil on the film‐forming properties and the effect of penetration enhancers on diffusion characteristics of indomethacin (IDM) drug through the castor‐oil‐based PU were investigated. Prolonged release of IDM was observed from the prepared PU patches. In vitro drug diffusion revealed that slow and prolonged release of IDM was achieved in the absence of penetration enhancers. The use of penetration enhancers showed a significant effect on drug diffusion. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 779–788, 2007     

Composite polymeric microsponge-based long-acting gel formulation for topical delivery of mupirocin

Topical delivery of medicaments in a controlled manner is still a promising area of research. Drug-containing dammar gum-ethyl cellulose composite microsponge loaded gel formulation (D-MSPG) was developed for controlled topical delivery of mupirocin. The drug-loaded microsponges (D-MSPs) were formulated by the quasi-emulsion solvent diffusion method and were evaluated for morphology, particle size distribution, entrapment efficiency, thermal properties, and crystallinity. The optimized D-MSPs (entrapment efficiency 91.5 ± 4.0% and particle size of 55.15 ± 2.9 μm) were dispersed in carbopol 934 gel (D-MSPG). The final product was characterized for pH, viscosity, texture, spreadability, consistency, syneresis, in vitro drug release, and ex vivo skin penetration study. A comparative study with marketed formulation was performed. For optimized gel formulation (G4), drug content was 104.19 ± 1.68%, and drug release was 84.19% after 24 h. The pH of the optimized gel was observed to be 6.05 ± 0.04. Viscosity of the optimized gel formulation was found to be 1212.15 ± 434.85 mPa-s at 50 s⁻¹. The steady-state flux (J) in ex vivo skin permeation was observed to be 53.96 μg cm⁻² h⁻¹ and the permeability coefficient was 2.69 cm/h for the optimized gel formulation. According to the findings, the D-MSPG-based formulation strategy can act well to prolong the topical delivery of mupirocin or similar drug molecules.     

In situ gel forming systems of poloxamer 407 and hydroxypropyl cellulose or hydroxypropyl methyl cellulose mixtures for controlled delivery of vancomycin

Poloxamers are a family of triblock copolymers consisting of two hydrophilic blocks of polyoxyethylene separated by a hydrophobic block of polyoxypropylene, which form micelles at low concentrations and form clear thermally reversible gels at high concentrations. The objective of this study was to develop an in situ gel forming drug delivery system for vancomycin using the minimum possible ratio of poloxamer 407 (P407). Decreasing the concentration of poloxamer could reduce the risk of hypertriglyceridemia induction. Different additives were added to the poloxamer formulations. It was observed that among different additives, hydroxypropyl methyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) can decrease poloxamer concentration required to form in situ gelation from 18 to 10%. The dynamic viscoelastic properties of the samples were determined. Both the storage modulus and the loss modulus of the samples increased abruptly as the temperature passed a certain point. The gelling temperature was in the order of P407 : HPC (10 : 10 w/w) < P407 : HPMC (10 : 10 w/w) < P407 : HPMC (15 : 5 w/w) < P407 : HPC (15 : 5 w/w). Drug release rate could be controlled by changing the type and ratio of additives as well as the amount of drug loaded. It can be concluded that combining P407 and cellulose derivatives could be a promising strategy for preparation of thermally reversible in situ gel forming delivery systems with low poloxamer concentration. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Development of ciprofloxacin hydrochloride loaded poly(ethylene glycol)/chitosan scaffold as wound dressing

A novel ciprofloxacin hydrochloride loaded chitosan/poly(ethylene glycol) (PEG) composite scaffold was developed for wound dressing application. PEG incorporation in chitosan scaffold showed enhanced loading up to 5.4 % and increased cumulative release of the drug up to 35 % as compared to pure chitosan scaffold (20 %). The drug loading and control release of the drug has been explained by the morphological features and drug–polymer/polymer–polymer interactions revealed by SEM, FTIR and DSC. Bacterial growth inhibition evaluation using Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus confirmed the efficacy of released drug from the scaffolds (pure and PEG mixed chitosan). Swelling study, bacterial penetration, moisture vapour transmission rate, haematocompatibility and biodegradation profile supported the suitability of scaffold used as wound dressing materials. In-vivo study on mice finally validated the controlled rate of drug release showing the effectiveness of PEG incorporation into the scaffold for quicker and regulated wound healing.     

Effects of formulation properties on sol–gel behavior of chitosan/glycerolphosphate hydrogel

Chitosan solution containing glycerolphosphate disodium salt (Gp) is an injectable thermosensitive in situ gel-forming system which undergoes sol–gel transition under certain physiological pH and temperature conditions. When a drug-incorporated chitosan/Gp solution is injected into the body, it forms a three-dimensional gel at 37 °C, which allows the drug to be released in a sustained manner. This hydrogel can be used as a drug delivery system for prolonged release of peptides and glycopeptides. The objective of this work was to investigate the effect of different excipients on the sol–gel behavior of this thermosensitive hydrogel. Chitosan polymeric solutions (2 % w/v) containing Gp and different excipients, such as hydroxypropyl methyl cellulose (HPMC), polyethylene glycol (PEG) with two different molecular weights (PEG200 and PEG1000), and poloxamer (F127) in various concentrations, were prepared, and the pH, sol–gel transition time, and syringeability of the final solutions were evaluated. The obtained results point to HPMC as the best additive for chitosan/Gp solutions in developing an in situ gel-forming drug delivery system with optimum gelling time. A significant decrease was noted in the sol-to-gel transition time (from 90 to 60 s) when HPMC was added to the system. This may have been due to the HPMC structure which acted as a viscosity-enhancing and gel-promoting agent. The in vitro release of vancomycin hydrochloride from chitosan/Gp/HPMC hydrogel was also studied. Vancomycin release studies showed a sustained release profile for over 20 days. It can be concluded that combining chitosan/Gp and HPMC is a promising strategy for preparing a thermally reversible in situ gel-forming delivery system with an optimized gelation time.     

Fabrication and Characterization of Matrix-Type Transdermal Patches Loaded with Ramipril and Repaglinide Through Cellulose-based Hydrophilic and Hydrophobic Polymers: In Vitro and Ex Vivo Permeation Studies

Transdermal patches loaded with ramipril and repaglinide were prepared with the ambition to develop matrix-type transdermal drug delivery system for enhanced permeability and hence improved bioavailability. Different formulations were designed by intermittent concentrations of hydroxypropyl methylcellulose K4M as hydrophilic polymer and ethyl cellulose as hydrophobic polymer. Solvent casting method was used for the fabrication of transdermal patches. Oleic acid and propylene glycol were used to enhance permeability along with polyethylene glycol 400 as plasticizer. Newly designed patches were then evaluated for various physicochemical and mechanical properties. Compatibility studies were performed by Fourier transformed infrared spectroscopy which did not reveal any interaction between drug and polymers. Crystalline nature of drugs was confirmed when they were subjected to X-ray diffraction study and surface morphological studies using scanning electron microscopy. Transdermal patches were of good mechanical strength with folding endurance of more than 300-fold and 100% flatness. Percent drug contents of ramipril and repaglinide ranged from 90 to 105%, i.e., analogous to official limits. In vitro and ex vivo permeation studies were executed using franz diffusion cell. The cumulative amount of drug permeated through skin was 55.22–112.72% for repaglinide and 73.14–91.46% for ramipril. The release behavior of the permeated drug was analyzed by the application of model-dependent approaches. The results showed that Korsmeyer–Peppas model was found to be dominating in most of the formulations and drugs followed diffusion mechanism. It could be concluded that hydroxypropyl methylcellulose K4M and ethyl cellulose has great potential for ramipril and repaglinide as a vector for transdermal drug delivery effectively because of the formation of smooth surfaces of patches, high folding endurance, and entrapment efficiency with the ability to release the drugs in sustained manner.     

Crosslinking of poly(N-vinyl pyrrolidone-co-n-butyl methacrylate) copolymers for controlled drug delivery

Poly(N-vinyl pyrrolidone-co-n-butyl methacrylate) P(NVP-co-nBMA) copolymers containing high N-vinyl pyrrolidone content were crosslinked to increase their hydro-stable nature for controlled drug delivery. Diethylene glycol dimethacrylate (DEGDMA) and trimethylolpropane trimethacrylate (TMPTMA) were used as crosslinkers. The effect of crosslinker concentration and functionality on gel content, thermal stability and water uptake at 37 °C was investigated. The gel contents and thermal stability increased while water uptake decreased with increasing concentration and functionality of crosslinker. The copolymer crosslinked by TMPTMA showed good mechanical properties. The porous network structure of the copolymers was confirmed by scanning electron microscopic studies. Dexamethasone was selected as a model drug and its controlled release was observed for 22 days from TMPTMA crosslinked copolymer (NB91-T2) film, whereas 96 % drug was released in 35 days for DEGDMA crosslinked copolymer (NB91-D2) film. The kinetics of 10 h drug release identified first-order drug release for NB91-D2 and Higuchi kinetics for NB91-T2. The initial 60 % drug release followed non-Fickian diffusion mechanism. These results indicate the future application of NB91-D2 and NB91-T2 copolymer films as a drug carrier for implant coatings.     

Preparation of stealth micellar nanoparticles of novel biodegradable and biocompatible brush copolymers with cholesteryl-modified PLA and PEG side chains

Novel amphiphilic brush copolymers, P(CPLAMA)-co-P(PEGMA), of cholesteryl poly(l-lactic acid) (CPLA) and poly(ethylene glycol) monomethyl ether (PEG) with determined hydrophobic/hydrophilic ratios were synthesized by the methacrylate (MA) macromonomer copolymerization method. Brush copolymers were prepared via both free radical polymerization (FRP) and atom transfer radical polymerization (ATRP). The copolymer compositions were determined by ¹H NMR spectroscopy. The synthesized copolymers were used to prepare the micellar nanoparticles with hydrophobic CPLA and hydrophilic PEG forming the core and shell, respectively. The critical micelle concentration (CMC) values of the samples produced by FRP (brush copolymer 1) and ATRP (brush copolymer 2) were estimated to be approximately 0.9 and 0.7 mg/L in aqueous solution by a fluorescence probe technique, respectively. The transmission electron microscopy (TEM) images of micelles of the brush copolymers 1 and 2 showed that micelles were spherical in shape with a mean diameter of 111 and 32 nm, respectively. The results showed that the size of micelles became larger with the increase of the molecular weight of polymer and the relative content of the hydrophilic PEG as well. The drug loading efficiency and drug-releasing properties of the micelles were investigated by using naproxen as a hydrophobic model drug. The in vitro release of naproxen-loaded micelles with about 85–89 % loading efficiency and 17–18 % loading capacity was studied by a using dialysis method in phosphate-buffered solution at 37 °C. The drug-releasing characteristics exhibited a phase of slow release. On the basis of the results obtained, the proposed brush copolymers may be useful in various targeted drug delivery applications, especially those involving hydrophobic drugs.     

Development of topical gel containing aceclofenac-crospovidone solid dispersion by “Quality by Design (QbD)” approach

This article describes the development, optimization, and evaluation of Carbopol 940 topical gel containing aceclofenac-crospovidone (1:4) solid dispersion using “Quality by Design (QbD)” approach based on 2³ factorial design. The effect of crospovidone, tri-ethanolamine, and ethyl alcohol amount on the drug permeation profile of the topical gel containing aceclofenac-crospovidone solid dispersion was optimized by 2³ factorial design. The optimized gel showed improved permeation profile with cumulative drug permeation of 26.262 ± 2.157%, and permeation flux of 0.059 ± 0.011 μg/cm²/h. These gels were characterized by pH, viscosity, gel strength and FTIR study. The in vivo anti-inflammatory activity of the optimized gel was evaluated in rats using carrageenan-induced rat-paw oedema model and found excellent anti-inflammatory comparable with a marketed gel without producing any skin irritation.     

Synthesis and evaluation of luliconazole loaded biodegradable nanogels prepared by pH-responsive Poly (acrylic acid) grafted Sodium Carboxymethyl Cellulose using amine based cross linker for topical targeting: In vitro and Ex vivo assessment

ABSTRACT

Fungal infection in immuno compromised patients causes skin syndromes and problems. At Present, innovative alternatives are required to cure skin disorders and infections. Luliconazole is a novel, broad spectrum, imidazole antifungal agent. The purpose of this study was to develop biodegradable, pH responsive, chemically cross-linked and Poly (acrylic acid) grafted sodium carboxymethyl cellulose nanogels. Nanogels had been synthesized to evaluate its applicability as an effective carrier of luliconazole for topical (skin) targeting. Chemically cross-linked sodium carboxymethyl cellulose-grafted-Poly acrylic acid (NaCMC-g-PAA) was synthesized from acrylic acid and sodium carboxymethyl cellulose using N, N’-methylene bisacrylamide (cross-linker) and potassium persulfate (initiator) using free radical polymerization. Variation of reaction parameters such as pH, cross linker, initiator and temperature has been used to optimize the best one. The developed nanogels reveal significant pH sensitive drug releasing behavior. NaCMC-g-PAA nanogels has been characterized using various physicochemical characterization techniques. Nanogels characteristics were evaluated through the In vitro drug release, Ex vivo permeation study, Nuclear magnetic resonance spectroscopy, Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscope, Stability Study and antifungal activity. All batches were characterized for particle size analysis and ranged from 78.82 nm to 190 nm. The viscosity of developed nanogels was found to be 5941 cps. It was observed that the developed drug-loaded NaCMC-g-PAA nanogels were more effective in killing the fungus. Consequently, Nanogels incorporated with luliconazole could be a new approach with improved antifungal activity and increased topical delivery for a drug with poor aqueous solubility rather than coarse drug-containing cream.     

Combination of viscosity regulator and frother to enhance low-rank coal flotation performance

This study investigated the synergistic effect of viscosity regulators (polyethylene glycol, sodium carboxymethyl cellulose, and polyacrylamide) and frother (2-octanol) on upgrading the flotation performance of low-rank coal. The results of flotation tests were consistent with the analysis of induction time and supported by the results of SEM, viscosity, foaming ability, and foam layer stability. In the present work, it was observed that the highest combustible matter recovery was obtained by mixing the polyethylene glycol (PEG300) with 2-octanol, which increased from 32.9% to about 64.4% accompanied by a little increase of ash content (0.54%). Therefore, it demonstrated that the combination of PEG300 and 2-octanol provided the highest combustible matter recovery and better flotation selectivity.     

Preparation and study of a thermo-responsive membrane using binary liquid crystal mixtures of cholesteryl cetyl ether and cholesteryl oleyl carbonate

A facile method for the synthesis of thermotropic liquid crystalline cholesteryl cetyl ether (CCE) was carried out from cholesterol and cetyl alcohol using montmorillonite K-10 as an acid catalyst. The aim of this study was to investigate the use of liquid crystalline blends of CCE and cholesteryl oleyl carbonate (COC) with appropriate crystal to smectic phase temperature (T _c?Cs) just above body temperature as a temperature-modulated drug permeation system. Using 30/70?mol ratio of COC/CCE, a mixture of desirable phase transition temperature was obtained. The phase transition behavior of COC/CCE binary liquid crystalline mixture was established by differential scanning calorimetry and polarizing optical microsopy. The COC/CCE-embedded cellulose nitrate membrane was used by an in vitro drug penetration studies. Paracetamol and mesalazine were chosen as hydrophobic and hydrophilic drug models, respectively. Paracetamol permeability through the membrane was higher at temperatures above the phase transition of liquid crystal (LC) blends (39?°C) than its permeability below the phase transition temperature of liquid crystal blends (30?°C). The drug penetration through LC-embedded cellulose membrane was influenced by the pore size of the membrane and therefore the adsorbed amount of LC. There was no penetration of mesalazine through that membrane presumably, due to the differences in hydrophilicity of LC-embedded membrane and permeated drug.     

Rheological characterization of chitosan matrices: Influence of biopolymer concentration

Viscoelastic properties of chitosan (CH), chitosan‐poly(ethylene glycol) 400 (CH‐PEG), and chitosan‐poly(ethylene glycol) 400 with glyoxal as crosslinking agent (CH‐PEG‐Gly) systems were studied to analyze the effect of chitosan concentration (from 0.83 to 1.67%). Dynamic moduli increase as chitosan concentration increases for all systems. For CH and CH‐PEG systems the loss modulus (G″) is greater than the storage modulus (G′) with predominance of the viscous over the elastic behavior. This corresponds to the characteristic behavior of solutions (nonstructured systems). The presence of PEG 400 induces a complementary reinforcement of the mechanical properties of the system. Except for the lowest chitosan concentration, when glyoxal was added to the CH‐PEG systems, a gelled matrix was obtained. In this case, G′ is greater than G″, and practically independent of frequency. This behavior is typical of three‐dimensional networks and indicates true gel formation, showing clear elastic behavior (tan δ < 1). In creep and recovery analysis, CH‐PEG‐Gly systems exhibited distinct regions that were mathematically modeled using Burger's model. This analysis shows that the CH‐PEG‐Gly matrices (from 1.25 to 1.67%) recover almost totally (100%). Therefore, these matrices could be useful as systems for the development of films for topical hydrophilic drug delivery, and the levels of the residual viscosity (η₀) or the complex viscosity (η*) could be used to control drug release. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Synthesis of a Series of Anionic Surfactants Derived from NP and their Properties as Emulsifiers for Reducing Viscosity of Highly Viscous Oil via Formation of O/W Emulsions

A series of alkyl phenol polyoxyethylene glycidyl ether (NP-n-O) and alkyl phenol polyoxyethylene ether hydroxypropyl sulfonate (NP-n-S) surfactants was synthesized to explore emulsification viscosity reduction. The optimum sulfonation conditions were obtained through orthogonal experiments, the ratio of alkyl phenol polyoxyethylene glycidyl ether and sodium bisulfite 1:1.5, 100 °C, and 6 h. The effects of concentrations of the synthesized surfactants, pH values, emulsifying temperature (40 and 60 °C) and water content on emulsification viscosity reduction and the stability of the emulsion to Venezuela’s Orinoco heavy oil were investigated. The water diversion ratio of emulsion at the reservoir temperature (55 °C) in 30 days was taken as an index, the results show that under the conditions of a temperature of 40 °C, an oil/water ratio of 7:3 and a surfactant NP-4-S concentration of 0.5 %, emulsions can be formed with a viscosity reduction rate reaching up to 99.69 % and with a water diversion ratio in 30 days reaching 9.38 %; while at 60 °C and an oil/water ratio of 7:3, at an NP-4-S concentration of 1 %, the viscosity reduction rate can reach 99.55 % and water diversion ratio is merely 4.23 % in 30 days. The mixture of NP-n-S, xanthan gum and cocamidopropyl dimethylamine oxide (CAO-30) at suitable concentration can greatly improve the emulsification viscosity reduction and emulsion stability, which gives an emulsion viscosity rate of over 98 %. Moreover, the emulsion can be stable for at least 30 days without water emerging.     

Development of pellets of nifedipine using HPMC K15 M and κ-carrageenan as mucoadhesive sustained delivery system and in vitro evaluation

Polymeric mucoadhesive pellets of nifedipine were designed using computer software and they were prepared by extrusion-spheronization using HPMC K15M and κ-carrageenan with microcrystalline cellulose. A randomized rotatable two factor central composite design was applied for assessment of influence of two independent variables such as concentration of κ-carrageenan and HPMC K15M on dependent variables. Pellets were characterized by FTIR, DSC, SEM, flow properties, particle size, abrasion resistance, sphericity, drug content, percent production yield, in vitro drug release, ex vivo mucoadhesion, stability studies and similarity factor. The optimized formulation was selected based on criteria of sphericity nearest to 1.0 with maximum cumulative drug release percentage. Formulation NF6 exhibited sufficient porous spheres, free flowing and smooth surface mucoadhesion of 91.34 % and drug content 98.22 ± 0.37 %. Kinetic modeling revealed that the formulation followed the Higuchi model and showed the Quassi-Fickian drug release mechanism. The similarity factor, F2 value, was found to be 74 ± 6 and there was no significant change in drug content and ex vivo mucoadhesion after 90 days at 40 ± 2 °C, and 75 ± 5 % RH clearly indicated the optimized batch NF6 was stable. Thus, it can be concluded that use of κ-carrageenan, microcrystalline cellulose and HPMC K15M at the 20:35:10 w/w ratio could provide an effective carrier for enhancement of sphericity and sustained release of matrix pellets.     

Thermosensitive biotinylated hydroxypropyl cellulose-based polymer micelles as a nano-carrier for cancer-targeted drug delivery

In this article, we report the synthesis of a novel amphiphilic hydroxypropyl cellulose-based polymer (HPC-PEG-Chol) that contained poly (ethylene glycol) and cholesterol-containing moieties with specific degrees of substitution. The resulting polymer was subsequently converted to a biotin conjugate (HPC-PEG-Chol-biotin), to develop a new potential cancer-targeted drug delivery system. The biotin conjugate was used to prepare micelles via the dialysis method. The polymeric micelles in aqueous solution presented a lower critical solution temperature (LCST) of 39.8 ^oC. The critical micelle concentration (CMC) values of the polymeric micelles at 25 and 45 °C were evaluated to be about 0.32 and 0. 25 g/L, respectively. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses of the micelles revealed the spherical shapes of the micelles, with 84 nm mean diameters that increased with the increase of the temperature above LCST. The hydrophobic anticancer drug paclitaxel (PTX) was loaded in the micelles and the in vitro release behaviors of PTX were investigated at different temperatures. The release profile of PTX from the polymeric micelles revealed a thermosensitivity, since its release rate was higher at 41 °C than at 37 °C. Fluorescent microscopy analyses confirm that the PTX-loaded HPC-PEG-Chol-biotin is superior in cellular uptake, with very strong adsorption to both HeLa and MDA-MB-231 cancer cell lines. MTT assay in normal cells indicated that HPC-PEG-Chol-biotin micelles have great potential to be safely used in tumor-targeting chemotherapy.     

Synthesis of pH-Responsive Multilayer Micelles for Sustained Release of Folic Acid

Two novel triblock copolymers poly(hydroxypropyl acrylate)-b-poly (methyl methacrylate)-b-poly(N,N-dimethylaminoethyl methacrylate) and poly(hydroxypropyl acrylate)-b-poly(methyl methacrylate)-b-poly(acrylic acid) were successfully synthesized. In acetone media, using the electrostatic interactions between N,N-dimethylaminoethyl methacrylate and acrylic acid units, they could form spherically shaped multilayer micelles with pH-responsive, and have a mean diameter around 110 nm. The critical micelle concentration of it was determined to be 2.42 mg/L. In vitro release experiments, the folic acid-loaded micelles exhibited sustained release behavior and the drug release rate was affected by the pH value of release media. These results indicate that the multilayer micelles may serve as a novel intelligent drug delivery system.     

Natural nanoporous silica frustules from marine diatom as a biocarrier for drug delivery

The possible use of natural silica nanoporous biomaterial from marine diatom for drug delivery applications was explored. Coscinodiscus concinnus have a homogeneous size distribution with radius of 220 ± 15 µm with surface featuring a mounded topography with about 2 µm wide porous domes organized on the surface in pentagonal packing. Streptomycin, used as a hydrophilic drug to demonstrate the in vitro oral drug delivery model based on diatom structure, mainly adsorbed on to the diatom silica surface (foramen), inside pores (cribrum) and into the internal hollow diatom structure (cribellum). The maximum drug loading capacity of streptomycin was 33.33 ± 2 %. The release was biphasic, involving initial burst release (first 6 h) mainly from the surface of diatom foramen, and sustained drug release (upto 7 days) from cribrum and cribellum. The study indicated that the live diatoms from marine environment, due to their unique features (easy cultivable, low-cost and biocompatibility), are a potential and alternative natural source of nanoporous siliceous material for in vitro oral drug delivery applications.     

Self-assembled micellar nanoparticles of a novel amphiphilic cholesteryl-poly(l-lactic acid)-b-poly(poly(ethylene glycol)methacrylate) block-brush copolymer

The biodegradable cholesteryl-(l-lactic acid) _n (CPLA) was synthesized via ring opening polymerization of l-lactide in the presence of cholesterol as an initiator and the catalytic amount of Sn(Oct)₂. The resulting monohydroxyl-terminated CPLA was subsequently converted to a bromine-ended macroinitiator (CPLA-Br) by esterification with 2-bromoisobutyryl bromide. Amphiphilic block-brush copolymers with different lengths of hydrophilic block (CPLA-b-P(PEGMA)₄ and CPLA-b-P(PEGMA)₁₂) were synthesized in a subsequent atom transfer radical polymerization of the poly(ethylene glycol)monomethyl ether methacrylate (PEGMA). The prepared polymers were characterized by FTIR, ¹H NMR and GPC. The self-assembly of the copolymers into the micellar aggregates in aqueous media was followed with dynamic light scattering, transmission electron microscopy and fluorescence analysis. The CMC values of the CPLA-b-P(PEGMA)₄ and CPLA-b-P(PEGMA)₁₂ samples were estimated approximately 56 × 10^?4 and 72 × 10^?4 g/L in an aqueous solution by fluorescence probe technique, respectively. The hydrophobic/hydrophilic chain ratio of the amphiphilic copolymers could have demonstrated a correlation with micelle formation ability and inter-micellar aggregation in an aqueous solution. Using the naproxen as a hydrophobic model drug, the drug-loading efficiency and drug release properties of the CPLA–PEG nanoparticles were investigated. In vitro release study of the naproxen-loaded micelles with about 54–60 % loading efficiency and 11–12 % loading capacity was performed using dialysis method in phosphate-buffered solution at 37 °C. Accordingly, these polymeric micelles may be provided as an effective drug carrier for drug controlled release by modulating the copolymer composition and molecular weight of blocks.