麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

温敏性乙二醇壳聚糖水凝胶的制备及药物缓释性能

以乙二醇壳聚糖为原料, 乙酸酐为酰化剂, 通过N-乙酰化反应, 制得了新型温敏性高分子乙酰化乙二醇壳聚糖. 通过核磁共振氢谱(¹H NMR)、 傅里叶变换红外光谱(FTIR)及试管倒置法对乙酰化乙二醇壳聚糖的结构及温敏性进行了表征, 通过扫描电子显微镜(SEM)和紫外-可见分光光度计(UV-Vis)对水凝胶的微观形貌和体外药物释放性能进行了研究. 结果表明, 随着反应时间和乙酸酐与乙二醇壳聚糖氨基摩尔比的增加, 产物的乙酰度逐渐增加; 乙酰化乙二醇壳聚糖溶液具有热可逆温敏性溶胶-凝胶转变行为, 可以通过控制乙酰化乙二醇壳聚糖的乙酰度和溶液浓度, 使溶胶-凝胶转变温度处于室温至体温(25~37 ℃)之间; 乙酰化乙二醇壳聚糖水凝胶具有“高度孔隙化且孔隙之间相互连通”的结构特点, 通过控制乙酰度和溶液浓度, 可使其孔径大小处于1~40 μm范围内; 乙酰化乙二醇壳聚糖水凝胶的乙酰度为89.90%时, 质量分数为5%~7%的水凝胶对抗癌药物吉西他滨具有缓释作用, 载药凝胶的释药时间可达3~5 d. 乙酰化乙二醇壳聚糖有望在药物释放及组织工程等领域得到广泛应用.     

Formulation of pH-sensitive aminated chitosan–gelatin crosslinked hydrogel for oral drug delivery

The objective of this study is to develop efficient pH-sensitive hydrogel based on aminated chitosan (AmCs) and gelatin (Gel) biopolymers for oral drug delivery. Herein, AmCs was chemically crosslinked with gelatin (Gel) biopolymer with different ratios, while their structures, thermal profiles and morphological properties were investigated by FTIR, TGA and SEM characterization tools, respectively. Moreover, gel-content, crosslinking density and rheological analysis were also performed. The results clarified that the developed AmCs-Gel crosslinked hydrogel displayed variable pH-sensitive swelling profiles. By increasing AmCs ratio, the swelling ratio was boosted at pH 1.2 and declined at pH 7.4. Besides, by increasing gelatin ratio in the hydrogel matrix, the loading efficiency of Oseltamivir phosphate (as a model of drug) was augmented and reached maximum value of 79.0% by AmCs-Gel (2:3) crosslinked hydrogel. The in vitro drug release profiles were investigated for 6 h in simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. Variable release profiles were realized depending on variation of AmCs and Gel ratios in the crosslinked hydrogel matrix. Finally, the formulated smart crosslinked AmCs-Gel hydrogels demonstrated acceptable biodegradability with no cellular toxicity, suggesting their applicability as pH-sensitive oral drug carriers.     

Preparation and characterization of poly(2-acrylamido-2-methylpropane-sulfonic acid)/Chitosan hydrogel using gamma irradiation and its application in wastewater treatment

Radiation grafting of chitosan with 2-acrylamido-2-methyl propane sulfonic acid (AMPS) has been successfully performed. The effect of absorbed dose (kGy) and the chitosan:AMPS ratio on graft hydrogelization was studied. The structure of the prepared hydrogel was confirmed using infrared spectroscopy (IR). Thermal properties were simultaneously studied by thermogravimetric analysis (TGA). The effect of the polymerization variables on the swelling % of the prepared hydrogel was investigated. The highest equilibrium degree of swelling (38.6 g/g) and gel % (94.7%) of the prepared chitosan–AMPS hydrogel was at 40% AMPS and absorbed dose of 10 kGy. The removal of methylene blue, acid red dye, Cd (II) and Cr (III) from composed wastewater was also investigated. The effect of pH, the chitosan:AMPS ratio and the concentration of the pollutant on the adsorption process were studied.     

Synthesis of cross-linked carboxymethyl cellulose and poly (2-acrylamido-2-methylpropane sulfonic acid) hydrogel for sustained drug release optimized by Box-Behnken Design

This research aims to fabricate and characterize chemically crosslinked CMC/PVP-co-poly (AMPS) based hydrogel for the sustained release of model drug metoprolol tartrate through the free radical polymerization technique. Box-Behnken Design was used to optimize CMC/PVP-co-poly (AMPS) hydrogel by varying the content of reactants such as; polymers (CMC and PVP), monomer (AMPS), and crosslinker (EGDMA). Carboxymethyl cellulose (CMC) was crosslinked chemically with AMPS with a constant ratio of PVP by the ethylene glycol dimethacrylate as the crosslinker in the presence of sodium hydrogen sulfite (SHS)/ammonium peroxodisulfate (APS) as initiators. After developing CMC-based hydrogels using different polymers, monomer, and crosslinker concentrations, this study encompassed dynamic swelling, sol–gel fraction, drug release and chemical characterizations such as FTIR, XRD, TGA, DSC, and SEM. In vitro drug release and swelling were performed at 1.2 and 6.8 pH to determine the sustained release pattern and pH-responsive behavior. These parameters depended on the crosslinker, polymer, and monomer ratios used in the formulation development. XRD, SEM, and FTIR showed the successful grafting of constituents resulting in the formation of a stable hydrogel. DSC and TGA confirmed the thermodynamic stability of the hydrogel. Hydrogel swelling was increased with an increase in the ratio of monomer; however, an increase in the ratio of polymer and crosslinker decreased the hydrogel swelling. In vitro gel fraction and drug release also depended on polymer, monomer, and crosslinker ratios. The fabricated CMC/PVP-co-poly (AMPS) hydrogels constituted a potential system for sustained drug delivery.     

Synthesis and Characterization of Cyclodextrin-containing Hydrogel for Ophthalmic Drugs Delivery

Hydrogel contact lenses are ideal drug carriers for ophthalmic drugs delivery. However, some drawbacks of traditional hydrogel restricted their application in the drug delivery field. Herein, we introduced chitosan and β-cyclodextrin (β-CD) into traditional hydrogel in order to improve the properties and control drug release. β-CD functionized and crosslinkable chitosan derivative (CCH) was synthesized and introduced into HEMA/NVP monomers to form HNC tripolymer hydrogel. The introduction of CCH accelerated the polymerization of monomers. Other properties such as equilibrium swelling ratio and oxygen transmissibility of HNC hydrogel were superior to that of HN hydrogel. The capacity of HNC hydrogel to resist the protein absorption was also superior to that of HN hydrogel. Hydrogels exhibited different capacity of drug loading and releasing for different drug.     

Preparation and properties of redox responsive modified hyaluronic acid hydrogels for drug release

A series of oxidized hyaluronic acid (oxi‐HA)/3,3′‐dithiobis (propionohydrazide) (DTP) redox responsive hydrogels by Schiff base reaction under physiological conditions were designed and prepared. The influence of the concentration of oxi‐HA and DTP on rheological properties, equilibrium swelling ratio, and degradation rate were investigated. All oxi‐HA/DTP hydrogels exhibited good rheological properties, high equilibrium swelling ratio, low degradation rate, and sustainable drug release properties, and the comprehensive performance of oxi‐HA5/DTP6 hydrogel was better than that of others. The redox responsiveness was evaluated by means of degradation and in vitro bovine serum albumin release behavior investigation with the stimulus of different concentration of dithiothreitol as reducing agent. The intelligent hydrogels could be potentially applied in the fields of drug delivery system, tissue engineering, or cell scaffold materials. Copyright © 2017 John Wiley & Sons, Ltd.     

Modified chitosan III,superabsorbency, salt‐ and pH‐sensitivity of smart ampholytic hydrogels from chitosan‐g‐PAN

Polyacrylonitrile (PAN) grafted chitosan was prepared by ceric‐initiated graft polymerization of acrylonitrile onto chitosan in a homogenous medium. The copolymer chitosan‐g‐PAN product was then hydrolyzed to yield a novel smart hydrogel (H‐chitoPAN) with superabsorbing properties. The influence of add‐on values as well as temperature and time of hydrolysis of the initial chitosan‐g‐PAN on swelling behavior of the hydrogel was evaluated in water and various salt solutions. The swelling kinetics of the superabsorbing hydrogel was studied as well. The hydrogels exhibited ampholytic and pH‐sensitivity characteristics. Several sharp swelling changes were observed in lieu of pH variations in a wide range (pH 2–13). The swelling variations were explained according to swelling theory based on the hydrogel chemical structure. Superabsorbency, pH‐ and salt‐sensitivity of the chitosan‐based hydrogel was briefly compared with the classical starch‐based superabsorbent, H‐SPAN. The pH‐reversibility and on–off switching behavior of the intelligent H‐chitoPAN hydrogels makes them good candidates for considering as potential drug carries. Copyright © 2004 John Wiley & Sons, Ltd.     

Fabrication and Properties of Porous Collagen/Hyaluronic Composite Scaffolds Containing Nano-Bioactive Glass for Tissue Engineering

In this work, nano-structured scaffolds were designed for tissue engineering using collagen, hyaluronic acid (HA) and nano-bioactive glass (NBAG) as their main components. The scaffold was prepared via freeze-drying method and the properties including morphology, porosity, compressive strength, swelling ratio and cytotoxicity in-vitro, were also evaluated. The composite scaffolds showed well interconnected macropores with the pore size of ranging from 100 to 500 μm. The porosity percent and swelling ability were decreased with the introduction of NBAG into the collagen/HA hydrogel; however, the compressive strength was enhanced. The cytotoxicity in-vitro study shows that the collagen-HA/NBAG scaffolds have good biocompatibility with improving effect on fibroblastic cells growth. It could be concluded that this scaffold fulfills the main requirements to be considered as a bone substitute.     

氯化钠相转变 K-型卡拉胶/聚 N-异丙基丙烯酰胺共混凝胶的辐射合成及性质研究

用γ辐射技术合成了K 型卡拉胶 (KC)与聚N 异丙基丙烯酰胺共混凝胶 (Blendgels) .合成产物透明 ,有弹性和较好的力学强度 .对不同条件下共混凝胶性能的测定结果表明 ,所形成的共混凝胶有明显的氯化钠相转变性质 ,也保持了聚N 异丙基丙烯酰胺 (PNIPAM)特有的温度敏感性 (LCST为 34℃ )     

Effect of organic and inorganic acids on chitosan/glycerophosphate thermosensitive hydrogel

The influence of organic and inorganic acids on chitosan/glycerophosphate (CS/GP) hydrogel has been investigated by dissolving chitosan in different acids. The results of gelation showed that all of the chitosan dissolved in monovalent acid solutions (i.e., formic, acetic, propionic, butyric, isobutyric, lactic, nitric, hydrochloric, and chloroacetic acid), when neutralized by GP solution, could transform into hydrogel after 2–5 min at 37 °C, while those dissolved in multivalent acids failed in gel formation. The inner structures of CS/GP hydrogels prepared with monovalent acids depended on the ionic strength and chain length of acids. Morphological examination by scanning electron microphotography demonstrated that large pores occurred during the gel-forming process, and the aperture size was also related to different acids. The cytotoxicity studies indicated that CS/GP systems prepared by dissolving chitosan in tested acids except chloroacetic acid were nontoxic to mouse embryonic fibroblasts and Hela cells.     

A fast on-demand preparation of injectable self-healing nanocomposite hydrogels for efficient osteoinduction

Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast(within 30 s) and easy gelation approach by reversible Schiff base formed between-CH=O of oxidized sodium alginate(OSA) and-NH_2 of glycol chitosan(GCS) mixed with calcium phosphate nanoparticles(CaP NPs).Its raw materials can be ready in large quantities by a simple synthesis process.The mechanical strength,degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of-CH=O and-NH_2.This hydrogel exhibits pH responsiveness,good degradability and biocompatibility.The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation,differentiation and osteoinduction in vitro.These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.     

Gelation time and degradation rate of chitosan-based injectable hydrogel

Gelation time and degradation rate of thermally-sensitive aqueous solutions of chitosan/Gp (glycerophosphate disodium salt) have been studied. The effects of different parameters such as Gp salt concentration, solution temperature, degree of deacetylation of chitosan (DDA) and drug loading on the gelation time have been investigated. Gravimetric analysis, gel permeation chromatography and FTIR spectrophotometry were used to investigate the influence of the DDA and concentration of chitosan solution on hydrogel degradation. The presented results indicated that gelation time decreases by increasing Gp salt concentration, temperature, concentration and DDA of chitosan solutions, while drug loading has no significant effect on gelation time. Slower degradation profile was recorded for hydrogel with the higher DDA and concentration of chitosan in the primary solution. FTIR studies indicated that the chemical structure of chitosan macromolecules does not change significantly during the degradation. It could be concluded that biodegradation of chitosan hydrogel occurred via its surfaces.     

Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Frontal polymerization as a new method for developing drug controlled release systems (DCRS) based on polyacrylamide

Stimuli-responsive polymers are macromolecular materials that undergo changes in response to small external stimuli in the environmental conditions. Among stimuli-responsive hydrogels are several polyacrylamides. Frontal polymerization is a fast, easy and inexpensive polymerization technique used for the synthesis of macromolecules.Aim of this work was the evaluation of the Frontal polymerization technique as new method for the preparation of controlled release dosage forms in which drug loading and polymer preparation occur together, as well as the possibility of obtaining more dosage units by a unique preparation. Hydrogels based on polyacrylamide containing diclofenac sodium salt were prepared using the Frontal polymerization and compared with similar systems obtained by the classic batch method. Polymers characterized by three different degree of cross-linking were prepared. The stability of the drug during the sample preparation was evaluated by IR analysis. The obtained samples were characterized in terms of drug content, morphology, in vitro drug release and swelling properties. Samples were studied also divided into disks. The results show that hydrogels based on polyacrylamide can be prepared by Frontal polymerization; these samples show similar properties to those obtained by batch polymerization. The drug is stable in the polymerization reaction conditions. Samples characterized by the lowest degree of cross-linking show drug loading values always higher than samples with the highest one regardless of the preparation method employed. The swelling ratio decreases as the degree of cross-linking increases. Loaded samples swell more than drug free ones. From a single preparation of hydrogel, three disks showing same drug content and in vitro release behaviour can be obtained and thus they can be used as three single dosage units.     

Surface modification by deposition of IPA plasma and gellan gum/chitosan hybrid hydrogel onto thermoplastic polyurethane for controlled release of N‐acetylcysteine

A thin film system composed of gellan gum and chitosan was fabricated through a combination of polyelectrolyte blend and hybrid hydrogel gelation for controlled release of drug. In this study, precursor isopropyl alcohol (IPA) was used to plasma deposit on the surface of thermoplastic polyurethane (TPU) to form a hydrophilic film. The features of the thin film were evaluated using water contact angle (WCA) measurement, scanning electron microscopy (SEM), Fourier transform infra‐red (FTIR), UV/Vis spectroscopy, and studies of controlled release of drugs. The hybrid hydrogel, pH‐sensitive, was tested at pH values of 1.2 and 7.4 of buffer solution and at a temperature of 37°C to observe its swelling ratio and drug delivery properties with N‐acetylcysteine as a drug material for controlled release. Furthermore, at pH 7.4, the hybrid hydrogel has an outstanding release ratio of up to about 90% absorption amounts of N‐acetylcysteine after 8 hr. The mechanism of drug release from thin film devices (n = 0.684) is anomalous (non‐Fickian) transport, the value of n lies between 0.43 and 0.85.     

Hydrogel Films Based on Chitosan and Oxidized Carboxymethylcellulose Optimized for the Controlled Release of Curcumin with Applications in Treating Dermatological Conditions

Cross-linked chitosan (CS) films with aldehyde groups obtained by oxidation of carboxymethyl cellulose (CMC) with NaIO₄ were prepared using different molar ratios between the CHO groups from oxidized carboxymethyl cellulose (CMCOx) and NH₂ groups from CS (from 0.25:1 to 2:1). Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy demonstrated the aldehyde groups’ presence in the CMCOx. The maximum oxidation degree was 22.9%. In the hydrogel, the amino groups’ conversion index value increased when the -CHO/-NH₂ molar ratio, cross-linking temperature, and time increased, while the swelling degree values decreased. The hydrogel films were characterized by scanning electron microscopy (SEM) and FTIR analysis. The curcumin encapsulation efficiency decreases from 56.74% to 16.88% when the cross-linking degree increases. The immobilized curcumin release efficiency (R_Ef%) and skin membrane permeability were evaluated in vitro in two different pH solutions using a Franz diffusion cell, and it was found to decrease when the molar ratio -CH=O/NH₂ increases. The curcumin R_Ef% in the receptor compartment was higher at pH = 7.4 (18%- for the sample with a molar ratio of 0.25:1) than at pH = 5.5 (16.5%). The curcumin absorption in the skin membrane at pH = 5.5 (47%) was more intense than at pH = 7.4 (8.6%). The curcumin-loaded films’ antioxidant activity was improved due to the CS presence.     

Swelling and Reswelling Characteristics of Cross-Linked Poly(vinyl alcohol)/Chitosan Hydrogel Film

Poly(vinyl alcohol) (PVA), hydrogel was prepared by using glutaraldehyde as a cross-linking agent. The blend semi-synthetic hydrogel film, consisting of PVA and chitosan, was prepared from a solvent-casting technique and characterized for their intermolecular interactions using infrared method. The swelling and reswelling behaviors, as well as mechanical properties of the synthetic and semi-synthetic gels were examined by weighing and tensile testing, respectively. Cross-linking the two types of polymer with glutaraldehyde produces a film with lower crystallinity and smaller swelling and reswelling degrees, but having improved mechanical properties. Also, the two types of films show a pH-dependent swelling characteristic. It was found that, the reswelling properties of synthetic hydrogels can be improved by blending PVA with certain ratio of natural polymer. This blending film, can be improve sandy soil properties for cultivation, such as, controlled release of water.     

聚富马酸丙二醇酯/羟基磷灰石复合多孔水凝胶的制备及其矿化性能研究

采用二步法合成了可降解的聚富马酸丙二醇酯(poly(propylene fumarate),PPF),并和N-乙烯基吡咯烷酮(N-vinyl pyrrolidone,NVP)共聚,以1,4-二氧六环为溶剂,通过改变溶剂的量制备了溶胀性能不同的PPF水凝胶.采用万能力学测试仪和扫描电子显微镜分别表征了水凝胶的压缩模量和形貌结构.选择20％ PPF和10％ NVP的聚合体系,预掺3％的纳米羟基磷灰石(hydroxyapatite,HA),以氯化钠粒子为致孔剂,制备了孔径在280～450 μm的纳米复合多孔水凝胶,使其压缩模量提高了61％.模拟体液矿化10天的结果显示,磷灰石成核位点的存在和良好的与外界液体环境物质交换的能力,促进了多孔水凝胶表面磷灰石的沉积,说明HA的复合可以有效提高PPF多孔水凝胶的成骨活性.     

Fabrication and characterization of poly(vinyl alcohol)/chitosan hydrogel thin films via UV irradiation

A series of poly(vinyl alcohol)/chitosan (PVA/CTS) hydrogel thin films were prepared via ultraviolet (UV) irradiation, with acrylic acid (AA) monomer added as a crosslinker without the addition of any other photo-initiator. The swelling behaviors, intermolecular chemical bonds, molecular structures, thermal behaviors, degrees of crystallinity, morphologies of the surfaces and internal structure, and their relationship to the AA content were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Poly(acrylic acid) (PAA) and its chemical crosslinks formed in hydrogel films via free-radical reactions were confirmed using FTIR and DSC analyses. The XRD patterns indicated that the degree of crystallinity of the hydrogel films decreased as the PAA content was increased. SEM micrographs showed that a uniform interconnected pore structure was formed through the entire hydrogel structure, and a gradient in the crosslinking density through the film thickness was observed to result from extended irradiation times. The swelling behaviors revealed that the formation of PAA and its crosslinking in the hydrogel thin films improved the pH stability and controlled the degree of swelling while retaining a high swelling rate. The successful formation of chemical crosslinking without any specific photo-initiator improves the natural characteristics of CTS and PVA and imparts the resulting PVA/CTS hydrogel thin films with properties that make them very promising in biomedical applications.