Evaluation of Polyvinyl Alcohol Hydrogel as a Sustained-Release Vehicle for Rectal Administration of Indomethacin

In order to evaluate an indomethacin poly vinyl alcohol (PVA) hydrogel for rectal administration, the in vitro release characteristics of indomethacin from the hydrogel and indomethacin plasma concentrations after rectal administration were examined. The PVA hydrogel containing indomethacin was prepared by a low-temperature crystallization method. The release of indomethacin from the PVA hydrogel agreed with the Fickian diffusion model for 10 hr. Rectal administration of indomethacin hydrogels to rats yielded high indomethacin plasma concentrations, without producing a sharp peak, and a sustained-release effect. In dogs, the indomethacin hydrogel produced a similar sustained-release effect; however, the indomethacin plasma concentration was relatively low compared with that of an indomethacin suppository.     

基于壳聚糖/海藻酸钠-聚乙烯醇的双层复合水凝胶膜伤口敷料研究

目的 制备聚乙烯醇（PVA）/海藻酸钠（SA）-聚乙烯醇（PVA）/壳聚糖（CS）双层（PAPCS）水凝胶膜伤口敷料，并进行质量评价。方法 将PVA与SA以质量比2∶1混合，配制PVA/SA混合溶液；将PVA与CS分别以质量比1∶1、2∶1、3∶1、4∶1、5∶1混合，配制不同质量比的PVA/CS混合溶液；采用涂布法制备PAPCS双层水凝胶膜伤口敷料。通过水蒸气透过率、溶胀性能、保水性、力学性能、体外凝血性能和血液相容性考察对水凝胶膜的性能进行评价、筛选PVA与CS质量比；通过傅里叶变换红外光谱检测（FTIR）和扫描电子显微镜（SEM）对PAPCS水凝胶膜的结构和形貌进行表征；通过抑菌实验比较PAPCS以及PAPCS复合载碘交联环糊精金属有机骨架（I₂@COF@PAPCS）的体外抗菌性能。结果 PVA与CS质量比为2∶1时，PAPCS水凝胶膜综合性能较好。PAPCS水凝胶膜为多孔结构，具有良好的溶胀性能、保水性以及力学性能；PAPCS水凝胶膜的水蒸气透过率为（2 643.76±91.62）g·m^-2·d^-1，接近理想范围；与PVA/SA相比，PAPCS的凝血指数显著降低（P＜0.01），为（72.93±3.58）%，溶血率小于5%，具有促进血液凝固的能力且血液相容性良好；与PVA/SA相比，PAPCS对于金黄色葡萄球菌、大肠埃希菌均有明显抑制作用，抑菌圈直径分别为（11.89±0.22）、（12.28±0.25） mm；I₂@COF@PAPCS对金黄色葡萄球菌、大肠埃希菌的抑菌圈直径分别为（21.95±1.47）、（18.89±0.81）mm，抑菌效果显著优于PAPCS（P＜0.001）。结论 采用涂布法可成功制备双层PAPCS水凝胶膜敷料，其各项性能指标良好，具有明显的凝血、抑菌效果，与I₂@COF复合使用，抑菌作用进一步增强。     

Synthesis of thermoresponsive composite hydrogel from Pluronic F127 reinforced by oil palm empty fruit bunches-extracted cellulose for silver sulfadiazine drug delivery

Hydrogels are modern dermal drug-delivery media which can hold a huge amount of water and modify their structure to enable spontaneous response to temperature change and are thus attractive to overcome the limitations of conventional drug-delivery media. In this study, a sustainable method was developed to synthesize thermoresponsive Pluronic F127 (PF127) composite hydrogel reinforced by cellulose extracted from oil palm empty fruit bunches (OPEFBs). The thermoresponsive cellulose/PF127 composite hydrogels were formulated by dissolving OPEFB-extracted cellulose in aqueous sodium hydroxide/urea solution prior to mixing with PF127 polymer at low temperature. The performance of the synthesized thermoresponsive cellulose/PF127 composite hydrogels was evaluated in terms of their swelling ratio, percentage of degradation, and in vitro silver sulfadiazine (AgSD) drug release. PCT20 thermoresponsive cellulose/PF127 composite hydrogel with 20 w/v% PF127 and 3 w/v% OPEFB cellulose showed high mechanical strength (storage modulus and complex viscosity values of 20.90 kPa and 2.09 kPa s, respectively), relatively high swelling ratio (3.63 ± 0.43), and prolonged release of AgSD (t_50% value of 4 h) compared with PCT17-PCT19 thermoresponsive cellulose/PF127 composite hydrogels. Besides, AgSD-loaded thermo-responsive cellulose/PF127 composite hydrogels showed relatively good inhibitory activity against the Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Streptococcus pyogenes, and Klebsiella pneumoniae bacteria. The exploration of thermoresponsive cellulose/PF127 composite hydrogel from OPEFBs can promote sustainable, environment-friendly, and cost-effective drug delivery systems by using abundant agricultural biomass.     

Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization,ex vivo permeation and in vivo biodistribution studies

Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L – made of Span^® 60 and Tween^® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol^® – as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100?µl of diluted formula with 50?µl saline having 200 MBq of ^99mTc and containing 13.6?mg of reducing agent (NaBH₄) and volume completed to 300?µl by saline at pH 10 for 10?min as reaction time. The biodistribution study showed that the transdermal ^99mTc-SF hydrogel exhibited a more sustained release pattern and longer circulation duration with pulsatile behavior in the blood and higher brain levels than the oral ^99mTc-SF dispersion. So, transdermal hydrogel of SF may be considered a promising sustained release formula for Hal maintenance therapy with reduced dose size and less frequent administration than oral formula.     

Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release

Abstract

A multiphase emulsification technique was modified in this process of microencapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locust bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60-65°C), microcapsules or ‘W/W particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50000-106000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7-4) at 37°C., showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial ‘burst' release of drug within 6h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions.     

Evaluation of ophthalmic suspensions using surface tension.

Uniformity and precision of single dose are required for ophthalmic suspensions including water-insoluble ingredients. Solid sediments formed after standing still must be immediately re-dispersible and distributed homogeneously before use. However, selection of an appropriate water-soluble polymer as suspending agent is a challenging problem. In this report, the relationship between the surface tension and the re-dispersibility of suspensions was investigated. The surface tension of 0.1 w/v% fluorometholone suspensions began to decline from 74 mN/m at 0.0001 w/v% of hydroxypropylmethylcellulose (HPMC) and became almost constant at 52 mN/m at 0.01 w/v% of HPMC. Re-dispersion time was less than 4 s when HPMC was present at concentrations between 0.0001 w/v% and 0.01 w/v%. At these concentrations, aggregation of suspended particles was not observed. When indomethacin suspensions at 1.0 w/v% concentration were used, the surface tension began to decline from 73 mN/m at 0.0005 w/v% HPMC and became constant at 50 mN/m at 0.005 w/v% HPMC. The suspension also showed good re-dispersibility, and a uniform suspension was obtained between 0.0005 w/v% and 0.005 w/v% of HPMC. The time required for re-dispersion was less than 17 s. The change of surface tension showed a good correlation with the concentration of HPMC in ophthalmic suspensions having good re-dispersibility. Measurement of the surface tension of suspensions provided the optimal concentration of the water-soluble polymers for the suspensions of well re-dispersible characteristics. Evaluation of ophthalmic suspension using surface tension is a good strategy for formulation of suspending pharmaceutical products in the ophthalmic area.     

Statistical optimization of indomethacin pellets coated with pH-dependent methacrylic polymers for possible colonic drug delivery

The objective of this study was to evaluate the effect of two factors (ratio of Eudragit S100 and Eudragit L100 and the coating level) on indomethacin release from pellets in order to optimize coating formulations for colonic delivery. Coating formulations were designed based on the full factorial design. Two independent variables were the ratio of Eudragit S100:Eudragit L100 (1:4, 1:1 and 1:0) and the level of coating (10%, 15% and 20%, w/w), respectively. The evaluated responses were lag time prior to drug release at pH 6.8 (the time required for drug release up to 2%) and percent of drug release at pH 6.8 in 5h. Polymers were coated onto the pellets containing 20% (w/w) indomethacin, using a fluidized bed coating apparatus. Dissolution test was carried out in media with different pH (1.2, 6.5, 6.8 and 7.2). The dissolution data revealed that the level of coating and the ratio of polymers are very important to achieve optimum formulation. Using responses and resulted statistical equations, optimum formulation consisted of Eudragit S100:L100 in 4:1 ratio and the level of coating (20%) was predicted. Practical results showed that the pellets prepared according to above formulation released no indomethacin at pH 1.2 (simulating stomach pH) and pH 6.5 (simulating proximal part of small intestine pH); drug release was slowly at pH 6.8 (simulating lower part of small intestine pH), but it was fast at pH 7.2 (simulating terminal ileum pH). The results of this study revealed that factorial design is a suitable tool for optimization of coating formulations to achieve colon delivery. It was shown that coating formulation consisted of Eudragit S100:Eudragit L100 in 4:1 ratio at 20% coating level has potential for colonic delivery of indomethacin loaded pellets. The optimized formulation produced dissolution profiles that were close to predicted values.     

The effect of taste masking agents on in situ gelling pectin formulations for oral sustained delivery of paracetamol and ambroxol

The aim of this study was to examine the influence of polyhydric alcohols (taste masking agents) on the rheological properties of in situ gelling pectin formulations and on the in vitro and in vivo release of paracetamol and ambroxol from these formulations. Gelation of orally administered pectin solutions containing calcium in complexed form occurred on release of calcium in the acidic environment of the stomach. Inclusion of 10% (w/v) sorbitol in 2% (w/v) pectin sols reduced the viscosity and ensured Newtonian flow properties. Xylitol and mannitol in similar concentrations were less effective in reducing viscosity; sucrose increased viscosity and caused non-Newtonian flow. The in vitro release of paracetamol from 2% (w/v) pectin gels formulated with 10% (w/v) of sorbitol, erythritol, xylitol or mannitol, and of ambroxol from 2% (w/v) pectin gels containing 10% (w/v) sorbitol, followed diffusion-controlled kinetics. Pectin gels (2%, w/v) containing sorbitol (10%, w/v) sustained the release of paracetamol in the rat stomach and bioavailabilities of approximately 90% of those from an orally administered paracetamol syrup were achieved. Sustained release of ambroxol from in situ gelling formulations was achieved with pectin concentrations of 1.5 and 1% (w/v) and a sorbitol concentration of 10% (w/v).     

Release characteristics of a model plasmid DNA encapsulated in biodegradable poly(ethylene glycol fumarate)/acrylamide hydrogel microspheres

Biodegradable hydrogel microspheres were synthesized by free radical suspension copolymerization of poly(ethylene glycol fumarate) macromer with bisacrylamide (PEGF/PAM). The acidic initiator ammonium persulphate in combination with the basic accelerator, N,N,N′,N′-tetramethyethylenediamine, were used to form the PEGF/PAM hydrogel at a neutral pH. The equilibrium water content of the microspheres was greater than 90% w/w. A model double stranded plasmid DNA (dsDNA) coding for the enhanced green fluorescence protein (pEGFP) gene was encapsulated in the hydrogel and the effect of loading and water content before swelling on release kinetics was investigated. Fluorescent confocal microscopy demonstrated that the encapsulated dsDNA was in the biologically active double stranded configuration. The highest loading of 0.81?mg?ml^?1 resulted in the best encapsulation efficiency of 95%. For that loading, 6% of the dsDNA was released in 25 days at a rate of 16?ng?ml^?1. The highest water content of 70% resulted in the highest burst release of 27% and 14% of the dsDNA was released in 25 days at a rate of 30?ng?ml^?1. For elucidating the release mechanism, the network mesh size was compared with the radius of gyration (R_g) of the dsDNA plasmid. The mesh size was 7?nm, which was less than R_g of the dsDNA (31?nm) but greater than the chain diameter of 1.1?nm. Since the mesh size was less than R_g, the release mechanism was by reptation of the segments of dsDNA within the tube formed by the network chains between crosslinks. These results indicate that the hydrogel mesh size and the size of the plasmid control the release mechanism.     

Injectable biodegradable temperature-responsive PLGA-PEG-PLGA copolymers: synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels

Injectable biodegradable temperature-responsive poly(DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with DL-lactide/glycolide molar ratio ranging from 6/1 to 15/l were synthesized from monomers of DL-lactide, glycolide and polyethylene glycol and characterized by 1H NMR. The resulting copolymers are soluble in water to form free flowing fluid at room temperature but become hydrogels at body temperature. The hydrophobicity of the copolymer increased with the increasing of DL-lactide/glycolide molar ratio. In vitro dissolution studies with two different hydrophobic drugs (5-fluorouracil and indomethacin) were performed to study the effect of DL-lactide/glycolide molar ratio on drug release and to elucidate drug release mechanism. The release mechanism for hydrophilic 5-fluorouracil was diffusion-controlled, while hydrophobic indomethacin showed an biphasic profile comprising of an initial diffusion-controlled stage followed by the hydrogel erosion-dominated stage. The effect of DL-lactide/glycolide molar ratio on drug release seemed to be dependent on the drug release mechanism. It has less effect on the drug release during the diffusion-controlled stage, but significantly affected drug release during the hydrogel erosion-controlled stage. Compared with ReGel system, the synthesized copolymers showed a higher gelation temperature and longer period of drug release. The copolymers can solubilize the hydrophobic indomethacin and the solubility (13.7 mg/ml) was increased 3425-fold compared to that in water (4 microg/ml, 25 degrees C). Two methods of physical mixing method and solvent evaporation method were used for drug solubilization and the latter method showed higher solubilization efficiency.     

Development of polyvinyl alcohol-sodium alginate gel-matrix-based wound dressing system containing nitrofurazone

Polyvinyl alcohol (PVA)/sodium alginate (SA) hydrogel matrix-based wound dressing systems containing nitrofurazone (NFZ), a topical anti-infective drug, were developed using freeze-thawing method. Aqueous solutions of nitrofurazone and PVA/SA mixtures in different weight ratios were mixed homogeneously, placed in petri dishes, freezed at -20 degrees C for 18h and thawed at room temperature for 6h, for three consecutive cycles, and evaluated for swelling ratio, tensile strength, elongation and thermal stability of the hydrogel. Furthermore, the drug release from this nitrofurazone-loaded hydrogel, in vitro protein adsorption test and in vivo wound healing observations in rats were performed. Increased SA concentration decreased the gelation%, maximum strength and break elongation, but it resulted into an increment in the swelling ability, elasticity and thermal stability of hydrogel film. However, SA had insignificant effect on the release of nitrofurazone. The amounts of proteins adsorbed on hydrogel were increased with increasing sodium alginate ratio, indicating the reduced blood compatibility. In vivo experiments showed that this hydrogel improved the healing rate of artificial wounds in rats. Thus, PVA/SA hydrogel matrix based wound dressing systems containing nitrofurazone could be a novel approach in wound care.     

壳聚糖-羧甲基壳聚糖凝胶的温敏性及体外药物缓释试验

目的研究壳聚糖/羧甲基壳聚糖/甘油磷酸钠（CS/CMCS/GPS）体系水凝胶的温敏性,载药凝胶以及共混β-环糊精（β-CD）包合物对药物的缓释性能。方法试管倒置法研究不同配比,不同pH值对CS/CMCS/GPS体系温敏凝胶化性能的影响;饱和水溶液法制备吲哚美辛/β-CD包合物,红外光谱表征包合物;紫外分光光度法测定包合物载药量和药物的累积释放度。结果 2%CS-2%CMCS-56%GPS体积比从10∶1∶2变为10∶10∶2（体系pH6.8）,37℃下凝胶化时间由370s升至490s,后又降至90s;三者体积比从10∶3∶1变为10∶3∶6（体系pH6.8）,37℃下凝胶化时间从407s降至66s。pH值在6.8~7.2范围适合于体系凝胶化。调节体积比及合适的pH值,在37℃下可实现CS/CMCS/GPS体系快速凝胶化。以吲哚美辛和吲哚美辛/β-CD包合物为模型药物,载有吲哚美辛温敏凝胶12h的累积释放度为65.2%,载有吲哚美辛/β-CD包合物温敏凝胶累积释放度为52.8%,而吲哚美辛原药12h的累积释放度为87.6%,吲哚美辛/β-CD包合物的累积释放度为82.1%。结论一定体积配比CS/CMCS/GPS体系在37℃具有快速凝胶特性,β-CD包合物与温敏性凝胶共混,对药物具有更加明显的缓释作用。     

Alginate-Based Hydrogel Containing Minoxidil/Hydroxypropyl-β-Cyclodextrin Inclusion Complex for Topical Alopecia Treatment

Cutaneous minoxidil (MXD) formulations were developed with the intent to reduce the side effects of the cosolvents propylene glycol and ethanol, frequently used in commercial MXD solutions. Completely aqueous alginate-based hydrogels were investigated and MXD aqueous solubility was improved using inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD) at 2 different molar substitution degree (MS), namely 0.65 and 0.85. HP-β-CD MS 0.65 was selected for its improved solubilizing ability toward MXD. At concentration of 39% w/v, this cyclodextrin increased the intrinsic aqueous solubility of MXD of about 22-fold. The calculated complexation constant was 2309 ± 20 M^?1, and the inclusion process was spontaneous and enthalpically driven. Nuclear magnetic resonance studies (Job plot, ¹H, 2D correlations spectroscopy, nuclear overhauser effect spectroscopy, and rotating-frame overhauser enhancement spectroscopy) confirmed the stoichiometry 1:1 between MXD and HP-β-CD providing information about the exact geometry of the inclusion complex. Rheological and in vitro release studies performed on the formulation loaded with MXD 3.5% w/w proved that the inclusion complex increased the viscosity of the hydrogel modulating the release of the free drug. Furthermore, the hydrogel formulation facilitate MXD to permeate into the skin and did not damage epidermis, suggesting that these completely aqueous MXD delivery systems can be proposed as alternative formulations to commercial solutions.     

Formulation and in vitro evaluation of topical nanosponge-based gel containing butenafine for the treatment of fungal skin infection

In the current study, four formulae (BNS1-BNS4) of butenafine (BTF) loaded nanosponges (NS) were fabricated by solvent emulsification technology, using different concentration of ethyl cellulose (EC) and polyvinyl alcohol (PVA) as a rate retarding polymer and surfactant, respectively. Prepared NS were characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). Nanocarrier BNS3 was optimized based on the particle characterizations and drug encapsulation. It was further evaluated for physicochemical characterizations; FTIR, DSC, XRD and SEM. Selected NS BNS3 composed of BTF (100 mg), EC (200 mg) and 0.3% of PVA showed, PS (543 ± 0.67 nm), PDI (0.330 ± 0.02), ZP (−33.8 ± 0.89 mV), %EE (71.3 ± 0.34%) and %DL (22.8 ± 0.67%), respectively. Fabricated NS also revealed; polymer-drug compatibility, drug-encapsulation, non-crystalline state of the drug in the spherical NS as per the physicochemical evaluations. Optimized NS (BNS3) with equivalent amount of (1%, w/w or w/v) BTF was incorporated into the (1%, w/w or w/v) carbopol gel. BTF loaded NS based gel was then evaluated for viscosity, spreadability, flux, drug diffusion, antifungal, stability and skin irritation studies. BNS3 based topical gels exhibited a flux rate of 0.18 (mg/cm².h), drug diffusion of 89.90 ± 0.87% in 24 h with Higuchi model following anomalous non-Fickian drug release. The BNS3 based-gel could be effective against pathogenic fungal strains.     

PVA-PEG physically cross-linked hydrogel film as a wound dressing: experimental design and optimization

The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze–thaw method. Response surface methodology with Box–Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze–thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12?hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze–thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation.     

Drug-carrier/hydrogel scaffold for controlled growth of cells

In this work, a novel functional drug-carrier/hydrogel scaffold was prepared to control the growth of cells for tissue engineering. The drug-carrier/hydrogel scaffold was constructed from a micelle/Ca-alginate microparticles (Alg-MPs)/poly(vinyl alcohol) (PVA) hydrogel composite. In such a system, paclitaxel (PTX) is encapsulated in the micelles formed by poly(l-glutamic acid)-b-poly(propylene oxide)-b-poly(l-glutamic acid) (GPG), while human vascular endothelial growth factor-165 (VEGF₁₆₅) is loaded in the Alg-MPs. The designed function of this scaffold is to encourage the fast growth of cells such as endothelial cells (ECs) in the early period to reduce the rejection and inhibit the growth of cells such as smooth muscle cells (SMCs) in late period to prevent the vascular intimal hyperplasia. The effect of VEGF₁₆₅ is to encourage the growth of ECs, while PTX is used to inhibit the growth of smooth muscle cells (SMCs). Structure characterizations show that the drug carriers are well dispersed in the PVA hydrogel. Independent release behaviors of the two drugs are observed. VEGF₁₆₅ shows a short-term release behavior, while PTX shows a long-term release behavior from the drug-carrier/hydrogel scaffolds. Further study shows a controllable cell growth behavior on this functional drug-carrier/hydrogel scaffold via the MTT assay.     

Superporous hydrogels based on blends of chitosan and polyvinyl alcohol as a carrier for enhanced gastric delivery of resveratrol

Resveratrol exhibits a number of pharmacological properties, notably antioxidant, anti-inflammatory and anti-cancer activities which are beneficial for the treatment of gastric diseases. However, the poor aqueous solubility and rapid metabolism are the important limitations in clinical uses. Superporous hydrogels (SPHs) based on chitosan/PVA blends were developed as a carrier for resveratrol solid dispersion (Res_SD) to increase the solubility and achieve sustained drug release in the stomach. The SPHs were prepared by gas forming method using glyoxal and sodium bicarbonate as cross-linking agent and gas generator, respectively. The solid dispersions of resveratrol with PVP-K30 were prepared by solvent evaporation and incorporated into the superporous hydrogels. All formulations showed rapid absorption of simulated gastric fluid and reached the equilibrium swollen state within a few minutes. The water absorption ratio and mechanical strength of SPHs were predominantly affected by the chitosan content, with maximum values at 1400 % and 375 g/cm², respectively.The Res_SD-loaded SPHs exhibited good floating properties and SEM micrographs revealed a highly interconnected pores structure with size around 150 μm. Resveratrol was efficiently entrapped within the SPHs at levels between 64 and 90 % w/w and efficient drug release was sustained over 12 h dependent on the concentration of chitosan and PVA. The Res_SD-loaded SPHs exhibited slightly less cytotoxic efffect towards AGS cells than pure resveratrol. Furthermore, the formulation showed similar anti-inflammatory activity against RAW 264.7 cells compared with indomethacin.     

Surface modified polymeric nanoparticles for immunisation against equine strangles

The successful development of particulate vaccines depends on the understanding of their physicochemical and biological characteristics. Therefore, the main purpose of this study was to develop and characterise stable surface modified poly(lactic acid) (PLA) nanoparticles, using polyvinyl alcohol (PVA), alginate (ALG) and glycolchitosan (GCS) containing a Streptococcus equi enzymatic extract adsorbed onto the surface. The characterisation of the preparations and a physicochemical study of the adsorption process were performed. The adsorption of S. equi proteins is a rapid process reaching, within 1 h, maximum adsorption efficiency values of 75.2 ± 1.9% (w/w) for PLA–PVA, 84.9 ± 0.2% (w/w) for PLA–GCS and 78.1 ± 0.4% (w/w) for PLA–ALG nanoparticles. No protein degradation was detected throughout the formulation procedures. As expected from a complex mixture of proteins, adsorption data suggest a Freundlich-type of equilibrium with regression coefficients (r²) of 0.9958, 0.9839 and 0.9940 for PLA–PVA, PLA–GCS and PLA–ALG, respectively. Desorption studies revealed a burst release within the first 6 h, for all formulations, followed by a sustained release profile. Nanoparticle surface modification with GCS improved the sustained release profile, as 20% of protein remained attached to the particle surface after 30 days. The results show that adsorption is an alternative method for the production of S. equi antigen carriers for vaccination purposes.     

壳聚糖/聚乙烯醇/甘油磷酸钠温敏性凝胶的制备及特性研究

目的:制备具有温敏性并具有一定强度的凝胶。方法:采用壳聚糖(CS)、聚乙烯醇(PVA)和甘油磷酸钠(GP)为基质,以CS的浓度(A)、CS与PVA质量比(B)及pH值(C)为考察因素,以初始凝胶化温度、凝胶强度和脱水情况为指标,采用正交设计优化凝胶处方,并进行验证试验。结果:优化处方为A20mg·mL-1、B1∶1、C7.2。所制凝胶水溶液在4℃和室温下为可流动的液体,于37℃、10min内可发生凝胶化,随温度升高凝胶化所需时间明显缩短,凝胶强度为1.4kPa,凝胶在体外降解过程中28d内pH值几乎不变。结论:CS/PVA/GP凝胶的制备工艺简单可行,并具有温敏性和一定强度。     

Effect of Peptide Loading and Surfactant Concentration on the Characteristics of Physically Crosslinked Hydrogel

The purpose of this study was to investigate the effect of varying drug load and concentration of a surfactant (sodium lauryl sulfate [SLS]) on the release characteristics of a model peptide (bovine serum albumin [BSA]), and study the net effects of the swelling properties of the hydrogel matrix [poly(vinyl alcohol) (PVA)]. The PVA hydrogel was prepared by a freeze-thaw process in the absence of a chemical crosslinking agent. The effect of protein loading on drug release was examined at three levels (0.65, 1.3, and 2%), whereas the effect of SLS was studied at four levels (0, 0.07, 0.13, and 0.26%). The baseline time for reaching equilibrium swelling was 48 hr for the hydrogel containing 0.65% BSA, and the equilibrium swelling time decreased significantly as the protein load was increased to 2%. The net effect of increased BSA concentrations resulted in faster BSA dissolution from the hydrogel matrix. The equilibrium-swelling ratio decreased from 21 to 10% when SLS was added to the PVA solution, which resulted in a reduction in the extent of equilibrium swelling; however, the time to reach equilibrium swelling was increased. The investigation provided a mechanistic basis toward the development of a hydrogel formulation by altering the concentration of two fundamental components, i.e., drug and surfactant, within the delivery system.