Drug-binding hydrogels of hyaluronic acid functionalized with beta-cyclodextrin

Hyaluronic acid (HA) hydrogels are attractive materials for biomedical applications because they are porous, water-swelling, biocompatible, biodegradable, and resistant to non-specific cell adhesion. A limitation of HA hydrogels is that incorporation of bioactive drugs can be restricted by low solubility of drug within the hydrogel environment. Our goal was to synthesize HA hydrogels that bind drug through hydrophobic interactions as a method for increasing drug loading. We functionalized photocrosslinked HA hydrogels with a methacryloyl derivative of beta-cyclodextrin (betaCD). betaCD is a molecular "basket" with a hydrophilic exterior and a hydrophobic cavity. Inclusion complexes are formed when betaCD hosts all or part of a hydrophobic drug within the cavity. HA hydrogels functionalized with methacryloyl-betaCD monomer gained the property of inclusion complexation which greatly enhanced the uptake of a model hydrophobic drug, hydrocortisone. Pre-incubation of the hydrogels with adamantane carboxylic acid (ACA) inhibited hydrocortisone uptake by competition for betaCD cavities. In addition, control hydrogels of HA functionalized with alphaCD monomer were not efficient at hydrocortisone uptake because the alphaCD cavity is too small for efficient complexation. These experiments confirmed that the betaCD monomer enhances drug loading by the mechanism of inclusion complexation. Drug-binding HA-betaCD hydrogels may be further engineered to create HA-based biomaterials with a built in drug delivery capability.     

Matrix Modifications Modulate Ophthalmic Drug Delivery From Photo-Cross-Linked Poly(propylene Fumarate)-Based Networks

In this work, different modifications of photo-cross-linked poly(propylene fumarate)/poly(N-vinyl pyrrolidone) (PPF/PNVP) matrices were studied for their effect on the release kinetics of two ophthalmic drugs. The hydrophilicity of solid PPF/PNVP matrices loaded with acetazolamide (AZ) or timolol maleate (TM) was increased by adding various amounts of poly(ethylene glycol) (PEG) or by increasing the amount of N-vinyl pyrrolidone (NVP) in the polymer mixture prior to cross-linking. The in vitro release studies that utilized high-performance liquid chromatography for quantification revealed highly accelerated drug release from the matrices with increasing contents of the hydrophilic modifier. AZ was released from matrices containing 5% PEG in 56 days, which equals approximately 25% of the release period found for the unmodified matrices. A comparable acceleration in drug release was found for TM-loaded samples modified with 5% PEG. These studies further revealed that 1% PEG is sufficient to shorten the TM release duration by one-third. A significant acceleration in drug release was also found for the samples that were fabricated from a PPF–NVP mixture with increased NVP content. Matrix water content and erosion were assessed gravimetrically. Micro-computed tomography was used to image structural changes of the release systems and shed light on the drug-release mechanism. This study showed that hydrophilic matrix modifications of PPF/PNVP matrices accelerate the drug release of two ophthalmic drugs and represent a suitable tool to adjust drug-release rates from PPF-based matrices for different therapeutic needs.     

Dissolution behaviour of hydrophilic matrix tablets containing two different polyethylene oxides (PEOs) for the controlled release of a water-soluble drug. Dimensionality study.

Hydrophilic matrix tablets containing polyethylene oxides as the retarding polymer have been successfully employed in the controlled release of drugs. To evaluate the relative influence of drug diffusion and polymer erosion mechanisms in the drug delivery process, we studied the hydration behaviour of matrix tablets containing a water-soluble drug and PEOs of two different molecular weights: Polyox WSRN 1105 (Mw = 0.9 x 10(6)) and Polyox WSRN 301 (Mw = 4 x 10(6)). The hydration rate, the extent of swelling, and the erosion rate of matrices containing the polymer, the drug and tableting excipients were evaluated in comparison to tablets made of pure polymer. The results of these studies on function of the release behaviour were then discussed. The results show that the higher molecular weight PEO swells to a greater extent and tends to form, upon hydration, a stronger gel, which is therefore less liable to erosion, if compared to the lower molecular weight PEO. This difference in the erosion behaviour can explain the different efficiencies of the two polymeric products in modulating the delivery rate of the water-soluble drug. Moreover, the presence of other soluble components (drug and excipients) in the dosage form enhances the erosion trend of the tablets with a consequent reduction of the efficiency of the polymer in drug release control.     

Modeling vancomycin release kinetics from microporous calcium phosphate ceramics comparing static and dynamic immersion conditions

The release kinetics of vancomycin from calcium phosphate dihydrate (brushite) matrices and polymer/brushite composites were compared using different fluid replacement regimes, a regular replacement (static conditions) and a continuous flow technique (dynamic conditions). The use of a constantly refreshed flowing resulted in a faster drug release due to a constantly high diffusion gradient between drug loaded matrix and the eluting medium. Drug release was modeled using the Weibull, Peppas and Higuchi equations. The results showed that drug liberation was diffusion controlled for the ceramics matrices, whereas ceramics/polymer composites led to a mixed diffusion and degradation controlled release mechanism. The continuous flow technique was for these materials responsible for a faster release due to an accelerated polymer degradation rate compared with the regular fluid replacement technique.     

A novel model and experimental analysis of hydrophilic and hydrophobic agent release from biodegradable polymers

Many factors affect the rate of drug release from biodegradable polymers. Here, we focus on investigating the effect of drug type on the degradation of P(DL)LGA 53/47 films and their ultimate release profiles. A freely water-soluble drug (metoclopramide monohydrochloride) exhibited an initial burst, whereas a water-insoluble drug (paclitaxel) exhibited an initial latent period with very little drug release. The onset of the second-stage release of the hydrophobic drug was delayed as compared with the hydrophilic drug. Overall, complete release of metoclopramide monohydrochloride was achieved much earlier than paclitaxel. In addition, the hydrophobic drug exhibited an extra stage of release when compared with the two-stage release for the hydrophilic drug. A novel model was developed to describe the underlying drug release mechanisms and kinetics. The model postulated that the total fraction of drug release from bulk-degrading polymer is a summation of three mechanisms: burst release, relaxation induced/drug-dissolution controlled release, and diffusional release. All the three steps are important for hydrophobic drugs. However, for hydrophilic drugs, burst and diffusional release steps are sufficient to account for the whole release process. The proposed model showed very good match with the experimental data.     

Control of cilostazol release kinetics and direction from a stent using a reservoir-based design

Sustained release formulations of a potent antithrombotic drug, cilostazol, in poly-(lactic acid-co-glycolic acid) (PLGA) matrices were created for luminal release from a novel drug-eluting stent utilizing reservoirs (RES TECHNOLOGY?). The crystallinity of cilostazol and the morphology of the cilostazol/polymer matrix in the stent reservoirs were examined by cross-polarized optical microscopy and differential scanning calorimetry. An in vitro method was developed to study release kinetics of various cilostazol formulations and to examine correlation with in vivo release. Formulation parameters such as drug-to-polymer ratio and the use of a polymer barrier on the abluminal surface of the drug/polymer matrix were found to be effective in modulating drug release rate. Cilostazol/PLGA(75/25) in the weight ratio of 50/50 to 70/30 displayed first-order release kinetics for the majority of the drug load. Addition of an abluminal polymer barrier slowed cilostazol release rate when compared to the bidirectional reservoir design. Excellent correlation between cilostazol in vivo release profile from stents in a porcine coronary artery model and that measured in vitro in a modified USP-7 apparatus suggests that the in vitro release system is capable of predicting in vivo release of cilostazol from stent reservoirs.     

Effect of Polymer Type on the Dynamics of Phase Inversion and Drug Release in Injectable In Situ Gelling Systems

The objective of this study was to evaluate the effect of the nature of the polymer on the dynamics of phase inversion and drug release in an in situ forming gel drug-delivery system composed of a biodegradable polymer and the solvent N-methyl-2-pyrrolidone (NMP), with metoclopramide monohydrochloride (metosalt) used as a low-molecular-weight model drug. Injection of this solution into an aqueous medium leads to the formation of a solid gel due to the rapid solvent/water exchange, followed by sustained release of the incorporated drug. The release of solvent from the injectable gel into phosphate buffer, which influences the polymer precipitation rate, was investigated as a function of the type of polymer using UV-Vis spectrophotometry. The cross-sectional gel morphology and its water uptake were characterized to relate the initial burst release (and thus the dynamics of phase inversion) to the polymer lactide/glycolide ratio and to the end-group characteristics. The results show that the phase inversion of hydrophobic polymers (e.g., PdlLA) occurs faster than the phase inversion of relatively more hydrophilic polymers (e.g., PLGA75/25, RG502 and RG502H). Three of the four polymers exhibit a four-phase profile, with the characteristics of each phase dependent on the hydrophobicity and degradation kinetics of the individual polymer.     

Artemisinin–Polyvinylpyrrolidone Composites Prepared by Evaporative Precipitation of Nanosuspension for Dissolution Enhancement

Nanoparticles of a poorly water-soluble anti-malarial drug, artemisinin (ART), and its composite particles with a hydrophilic polymer, polyvinylpyrrolidone (PVP), were synthesized using a nanofabrication method called the evaporative precipitation of nanosuspension (EPN). ART nanoparticles and ART/PVP composite particles containing ART nanoparticles coated with PVP were successfully prepared with the aim of improving the dissolution rate of ART. The effect of polymer concentration on the physical and morphological properties, and dissolution rate of the EPN-prepared ART/PVP composite particles was investigated. The crystallinity of ART nanoparticles decreased with increasing polymer concentration, as suggested by the differential scanning calorimetry and X-ray diffraction studies. The phase solubility studies revealed an A_L-type of curve, indicating a linear increase in the drug solubility with PVP concentration. The dissolution of the ART nanoparticles and ART/PVP composite particles markedly increased as compared to that of the original ART powder due to lower particle size and reduced crystallinity of the drug particles. The percent dissolution efficiency (DE), relative dissolution (RD), t _75% and similarity factor (f ₂) were calculated for the statistical analysis. Various mathematical models, viz., zero-order, first-order, Korsemeyer–Peppas and Higuchi, were applied to fit the experimental drug-dissolution data and diffusion was found to be the drug release mechanism.     

Design and release kinetic pattern evaluation of indomethacin microspheres intended for oral administration

Indomethacin has been incorporated into either ethylcellulose (EC) or Eudragit RL microspheres by a solvent-evaporation process. Production variables have been tested in an attempt to produce indomethacin microspheres having adequate oral controlled-release properties. In spite of high drug content in the ethylcellulose microspheres, the indomethacin release rate was too slow and incomplete. Although the addition of an hydrophilic polymer, polyethylene glycol), to the EC polymer enhanced the indomethacin release rate, it was not possible to reach release profiles suitable for oral use. Therefore, indomethacin was incorporated into a more permeable polymer, Eudragit RL. While incorporation efficiency decreased with increasing initial concentration of indomethacin, adequate oral-release profiles were achieved. It was found that all the global-release profiles yielded by the indomethacin-loaded Eudragit RL microspheres conformed to the Higuchi diffusional model of dispersed drug particles in spherical micromatrices and not to the desorption kinetic model of a dissolved drug from a monolithic spherical device.     

Effect of polymer type on the dynamics of phase inversion and drug release in injectable in situ gelling systems

The objective of this study was to evaluate the effect of the nature of the polymer on the dynamics of phase inversion and drug release in an in situ forming gel drug-delivery system composed of a biodegradable polymer and the solvent N-methyl-2-pyrrolidone (NMP), with metoclopramide monohydrochloride (metosalt) used as a low-molecular-weight model drug. Injection of this solution into an aqueous medium leads to the formation of a solid gel due to the rapid solvent/water exchange, followed by sustained release of the incorporated drug. The release of solvent from the injectable gel into phosphate buffer, which influences the polymer precipitation rate, was investigated as a function of the type of polymer using UV-Vis spectrophotometry. The cross-sectional gel morphology and its water uptake were characterized to relate the initial burst release (and thus the dynamics of phase inversion) to the polymer lactide/glycolide ratio and to the end-group characteristics. The results show that the phase inversion of hydrophobic polymers (e.g., PdlLA) occurs faster than the phase inversion of relatively more hydrophilic polymers (e.g., PLGA75/25, RG502 and RG502H). Three of the four polymers exhibit a four-phase profile, with the characteristics of each phase dependent on the hydrophobicity and degradation kinetics of the individual polymer.     

Effect of molecular weight and polydispersity on kinetics of dissolution and release from ph/temperature-sensitive polymers

N-isopropylacrylamide (NIPAAm) polymers exhibit a lower critical solution temperature (LCST). Aqueous solutions of these polymers are soluble below their LCST and precipitate above their LCST. The LCST is dependent on pH for polymers with ionizable groups because of a change in hydrophilicity with ionization and electrostatic repulsion that cause a shift in the LCST. We have designed a novel polymeric delivery system that utilizes linear, pH/temperature-sensitive terpolymers of NIPAAm, butyl methacrylate (BMA) and acrylic acid (AA). This system allows the aqueous loading of drugs in polymeric beads with high loading efficiency while preserving the bioactivity of the protein drug. Furthermore, the unique properties of the pH/temperature-sensitive polymeric bead make it a potential system for oral drug delivery of peptide and protein drugs to different regions of the intestinal tract. This study aims at investigating the effect of polydispersity and molecular weight (MW) of terpolymers of poly(NIPAAm-co-BMA-co-AA) with feed mol ratio of NIPAAm/BMA/AA 85/5/10 on the polymer dissolution rate and on the release kinetics of a model protein, namely insulin. Varying the weight average MW (Mw) and polydispersity of the polymer modulated the polymer dissolution rate and the release rate of insulin from pH/temperature-sensitive polymeric beads. An increase in the polydispersity of the polymer through the addition of high MW polymer chains caused a decrease in the release rate of insulin and in the polymer dissolution rate. High MW polymer chains impose a certain degree of interaction between polymer chains due to chain entanglement. There is a limiting value of MW above which chain entanglement has no effect on drug release rate.     

Cellulose acetate butyrate microcapsules containing dextran ion-exchange resins as self-propelled drug release system

Sulfopropylated dextran microspheres (SP-Ms), (Dm = 80 microm) loaded with a water soluble drug (Tetracycline HCl), were included in cellulose acetate butyrate (CAB) microcapsules. Spherical CAB microcapsules were obtained by oil in water (o/w) solvent evaporation method in the presence of an inert solvent as cyclohexane (CyH) or n-hexane (N-Hex), and different excipients (Phospholipon, Tween, Span, Eudragit RS 100). Chloroform was found to be the best solvent for the preparation of the microcapsules. Also, the sphericity as well as the porosity of the microcapsules was controlled by the presence of an inert solvent. The final concentration of the drug in CAB microparticles was up to 25% (w/w). The key factors for the successful preparation were also the viscosity of the polymer, while the wettability of the resulted microcapsules, the temperature of the preparation, and the porosity have modulated the release of the drug. The higher is the amount of encapsulated microspheres the thinner is the CAB wall between the compartments created by their incorporation. When these microspheres come in contact with the release medium, the pressure created by their swelling breaks the polymer film and the drug starts to be released. The more drug is released in phosphate buffer the higher is the swelling degree of the encapsulated ion exchange resins and the force created by their supplementary swelling will break the more resistants walls. In this way a self-propelled drug release is achieved, until almost all drug was eliberated.     

Structured drug-eluting bioresorbable films: microstructure and release profile

Bioresorbable drug-eluting films can be used in many biomedical applications. Examples for such applications include biodegradable medical support devices which combine mechanical support with drug release and antibiotic-eluting film coatings for prevention of bacterial infections associated with orthopedic implants or during gingival healing. In the current study, bioresorbable drug-loaded polymer films are prepared by solution processing. Two film structures are studied: A polymer film with large drug crystals located on its surface (A-type) and a polymer film with small drug particles and crystals distributed within the bulk (B-type). The basic mode of drug dispersion/location in the film (A or B-type) is found to be determined mainly by the process of film formation and depends mainly on the solvent evaporation rate, whereas the drug's hydrophilicity has a minor effect on this structuring process. Most release profiles from A-type films exhibit a burst effect of approximately 30% and a second release stage that occurs at an approximately constant rate and is determined mainly by the polymer weight loss rate. An extremely high burst release is exhibited only by a very hydrophilic drug. The matrix (monolithic) nature of the B-type film enables release profiles that are determined mainly by the host polymer's degradation profile, with a very low burst effect in most of the studied systems. In addition to the drug location/ dispersion in the film, the host polymer and drug type also strongly affect the drug's release profile from the film. It has been demonstrated that appropriate selection of the process parameters and film components (polymer and drug) can yield film structures with desirable drug release behaviors. This can lead to the engineering of new bioresorbable drug-eluting film-based implants for various applications.     

Biocompatibility and drug release behavior of spontaneously formed phospholipid polymer hydrogels

Hydrogels containing 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties were formed from aqueous solutions with water-soluble MPC polymers with carboxylic acid and alkyl groups because of hydrogen bonding formation. To investigate the biocompatibility and drug release behavior of the hydrogels, we used random- and block-type carboxylic acid MPC polymers, such as poly [MPC-co-methacrylic acid (MA)] (rPMA), poly[MPC-co-4-(2-methacryloyloxyethyl) trimellitic acid (MET)] (rPMT), poly (MA-block-MPC-block-MA) (bPMA) and poly(MET-block-MPC-block-MET) (bPMT), and alkyl MPC polymers, such as poly[MPC-co-n-butyl methacrylate] (PMB) and poly(MPC-co-benzyl methacrylate) (PMBz). We investigated the biocompatibility of the spontaneously formed MPC polymer hydrogels by a hemolysis test and an in vivo injection test. The random MPC polymers having carboxylic acid groups expressed more hemolytic activity compared to the block polymers. The results of the in vivo injection test also indicated low biocompatibility of the carboxylic acid polymers especially at high concentration. The alkyl MPC polymers, the PMB and PMBz showed excellent biocompatibility in both hemolysis and in vivo injection test. However, the hydrogels, the rPMA/PMB hydrogel (rABgel) and the rPMT/PMBz hydrogel (rTZgel) lowered the hemolytic activity of elemental polymers, the rPMA and rPMT. Thus, suppression of the ionization of the carboxylic acid groups is necessary for biocompatibility. We also investigated the drug release behavior with attention to the interaction between the polymer and the drugs. The release behavior of a relatively low-molecular-weight hydrophilic drug, 5-fluorouracil, did not depend on the structure of the polymers. The higher-molecular-weight drugs, ketoprofen and indomethacin, were released faster from the block polymer hydrogel than the random polymer hydrogel, the rABgel, while the highest-molecular-weight drug, doxorubicin, was released faster from the random polymer hydrogel. A probable reason for this is the difference in the molecular structure; that is, the separated hydrophilic and hydrophobic sections in the block polymers constructed pathways where a drug can diffuse. In addition, the rTZgel suppressed the release of a drug with a large number of aromatic rings probably because of the stacking effect. The results of the compression test also suggested the existence of the stacking effect between the rTZgel and the drugs. Based on these results, control of drug release is possible by selecting a reservoir with an appropriate chemical structure to interact with the drug. For example, release of a relatively linear-structured drug with less aromatic rings can be suppressed in the rABgel rather than in the rTZgel. Thus, it can be concluded that if the ionization is suppressed, these MPC polymer hydrogels can be used as a material for a drug reservoir that can be selected according to the drug.     

Time-controlled pulse-drug release from dry-coated wax matrix tablets for colon drug delivery

This study aimed to prepare a colon drug delivery system using dry-coated time-controlled disintegration wax matrix tablets. Indomethacin was used as a model drug. Behenic acid and lactose were used as coating materials. The effects of lactose content and pH of the dissolution medium on drug release were investigated. The porosity and the tortuosity of the surface matrix layer were calculated. Four formulations of wax matrices containing different percentages of lactose in the surface layer, i.e. 70, 65, 60 and 55, were prepared. The lag times of indomethacin release from the matrices in 0.05 M phosphate buffer pH 7.4 were 50, 162, 294 and 539 minutes for formulations containing 70, 65, 60 and 55% lactose, respectively. The release of drug from formulations containing lactose in the range of 60-70% in different media, i.e. 0.05 M phosphate buffer pH 7.4, 0.05 M alkaline borate buffer pH 8.5 and in the case of pH changed media from pH 1.3 to pH 7.4, was not different (p=0.1). This implies that the different environment in the gastro-intestinal tract will not affect the release of this delivery device. The required lag time period can be met by varying the amount of lactose.     

Physico-chemical considerations in the development of an ocular polymeric drug delivery system

A silicone-based prepolymer was used as the major component for the fabrication of novel ocular devices. Gentamicin sulphate was used as a probe drug, due to its high aqueous solubility and widespread application. Mechanical properties of films containing the drug before and after gamma sterilization and exposure to heat were found to be unchanged. The hydrolytic stability of the polymer films was uncompromised by gamma sterilization. However, high pressure liquid chromatography analysis of the drug released from polymer matrices exposed to heat for long time periods indicated a small amount of degradation. The drug release rates of the devices were found to be affected by gamma irradiation and exposure to heat.     

Sucrose esters with various hydrophilic–lipophilic properties: Novel controlled release agents for oral drug delivery matrix tablets prepared by direct compaction

Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic–lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic–lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic–lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic–lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3–16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System.     

Polymers for the controlled release of macromolecules: effect of molecular weight of ethylene-vinyl acetate copolymer

Matrices composed of ethylene-vinyl acetate copolymer (EVAc) have been used for controlled delivery of macromolecular bioactive agents. Three EVAc samples of different molecular weight (MW) were selected from solution fractionated samples. The polymer MW is a sensitive factor in affecting the release rate of bovine serum albumin (BSA); the higher the MW of EVAc, the slower the release rate. Depending on the degree of hydrophilicity of the device, the relatively hydrophilic drug particles would cause various degrees of swelling pressure upon water uptake. The relatively hydrophobic EVAc carrier would impose different degrees of restrictive force as determined by polymer MW. The interaction between the restrictive force of the carrier and the swelling pressure of the drug particles is a key factor in affecting the drug release kinetics. As a result, the selection of the polymer carrier can be used to affect the kinetics of a controlled release device.     

Effect of molecular weight and polydispersity on kinetics of dissolution and release from pH/temperature-sensitive polymers

N-isopropylacrylamide (NIPAAm) polymers exhibit a lower critical solution temperature (LCST). Aqueous solutions of these polymers are soluble below their LCST and precipitate above their LCST. The LCST is dependent on pH for polymers with ionizable groups because of a change in hydrophilicity with ionization and electrostatic repulsion that cause a shift in the LCST. We have designed a novel polymeric delivery system that utilizes linear, pH/temperature-sensitive terpolymers of NIPAAm, butyl methacrylate (BMA) and acrylic acid (AA). This system allows the aqueous loading of drugs in polymeric beads with high loading efficiency while preserving the bioactivity of the protein drug. Furthermore, the unique properties of the pH/temperature-sensitive polymeric bead make it a potential system for oral drug delivery of peptide and protein drugs to different regions of the intestinal tract. This study aims at investigating the effect of polydispersity and molecular weight (MW) of terpolymers of poly(NIPAAm-co-BMA-co-AA) with feed mol ratio of NIPAAm/BMA/AA 85/5/ 10 on the polymer dissolution rate and on the release kinetics of a model protein, namely insulin. Varying the weight average MW (M_w) and polydispersity of the polymer modulated the polymer dissolution rate and the release rate of insulin from pH/temperature-sensitive polymeric beads. An increase in the polydispersity of the polymer through the addition of high MW polymer chains caused a decrease in the release rate of insulin and in the polymer dissolution rate. High MW polymer chains impose a certain degree of interaction between polymer chains due to chain entanglement. There is a limiting value of MW above which chain entanglement has no effect on drug release rate.     

pH敏感性羟乙基甲壳素/聚丙烯酸水凝胶的制备及其释药性能研究

用氯乙醇对甲壳素进行醚化改性，得到水溶性羟乙基甲壳素（Hydroxyethyl chitin，HECH），用化学交联法制备了由聚丙烯酸（PAA）和HECH复合的互穿网络（IPN）水凝胶。溶胀实验表明：该水凝胶在人工肠液（pH7．4，I=0．1）中的溶胀度远大于在人工胃液（pH）．4，I=0．1）中的溶胀度，凝胶的溶胀度随着温度的升高而增大；以该凝胶制备了双氯芬酸钾缓释体系，释放实验表明该凝胶具有较好的缓释性能。