Structure and control release of chitosan/carboxymethyl cellulose microcapsules

Microcapsules of chitosan/sodium carboxymethyl cellulose (NaCMC) were successfully prepared using a novel method of emulation phase separation. Their structure and morphology were characterized by infrared spectroscopy (IR), scanning electron microscopy (SEM), and X-ray diffraction. Bovine serum albumin (BSA) was encapsulated in the microcapsules to test their release behavior. The swelling behavior, encapsulation efficiency, and release behavior of the microcapsules with different chitosan contents and pH conditions were investigated. The results indicated that the microcapsules have a high encapsulation efficiency (75%) and a suitable size (20–50 μm). The BSA in the microcapsules was speedily released at pH 7.2, namely, in intestinal fluid. The BSA release was reduced with increase of the chitosan content from 17 to 38% in the microcapsules. Acid-treated microcapsules have a compact structure, owing to a strong electrostatic interaction caused by —NH₂ groups of chitosan and —COOH groups of CMC, and the encapsulated BSA was hardly released at pH 1.0, namely, in gastric juice. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 584–592, 2001     

Polyelectrolyte complex beads composed of water‐soluble chitosan/alginate: Characterization and their protein release behavior

Polyelectrolyte complex (PEC) beads were prepared from water‐soluble chitosan (WSC) and alginate complex solution with different ratios by dropping method, and all procedures used were performed in aqueous medium at neutral environment. The structure and morphology of the beads were characterized by IR spectroscopy and scanning electron microscopy (SEM). IR spectroscopy confirmed the electrostatic interactions between amino groups of WSC and carboxyl groups of alginate. SEM showed internal section of the PEC bead, which had porous structure compared with compact structure of alginate beads. The swelling behavior, encapsulation efficiency, and release behavior of bovine serum albumin (BSA) from the beads at different pHs were investigated. PEC beads demonstrated different responses to pH from alginate beads. The ratio of WSC to alginate influenced the encapsulation and release of BSA. At pH 1.2, small amount (< 15%) of BSA was released from the PEC beads except AC12. However, at pH 7.4, a large amount (> 80%) of BSA was released from AL in the first 3 h due to the rapid disintegration of the beads, whereas BSA release was retarded from complex beads due to the forming of PEC. The results suggested that the WSC/alginate beads could be a suitable polymeric carrier for site‐specific protein drug delivery in the intestine. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4614–4622, 2006     

Chitosan/calcium–alginate beads for oral delivery of insulin

A mild chitosan/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as albumin and insulin, was investigated. The microcapsules were derived by adding dropwise a protein-containing sodium alginate mixture into a chitosan–CaCl₂ system. The beads containing a high concentration of entrapped bovine serum albumin (BSA) as more than 70% of the initial concentration were achieved via varying chitosan coat. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within 24 h and no significant release of BSA was observed during treatment with 0.1M HCl pH 1.2 for 4 h. But the acid-treated beads had released almost all the entrapped protein into Tris-HCl pH 7.4 media within 24 h. Instead of BSA, the insulin preload was found to be very low in the chitosan/calcium alginate system; the release characteristics were similar to that of BSA. From scanning electron microscopic studies, it appears that the chitosan modifies the alginate microspheres and subsequently the protein loading. The results indicate the possibility of modifying the formulation in order to obtain the desired controlled release of bioactive peptides (insulin), for a convenient gastrointestinal tract delivery system. © 1996 John Wiley & Sons, Inc.     

Preparation and evaluation of alginate/chitosan microspheres containing pheromones for pest control of Megaplatypus mutatus Chapuis (Platypodinae: Platypodidae)

This work describes the optimization of an alginate/chitosan microsphere preparation for the encapsulation of a sexual pheromone, 6‐methyl‐5‐hepten‐2‐ol (sulcatol), to realize a slow‐release device for the biological control of the Megaplatypus mutatus pest. To evaluate and select the best encapsulation/release conditions three parameters were studied: alginate concentration, pH of gelling solution and Ca²⁺/COO^? ratio. The preparation was optimized using biopolymers with improved mechanical properties and swelling behavior. The obtained microspheres were characterized using Fourier transform infrared spectroscopy, scanning electron and optical microscopies, swelling degree, mechanical properties and in vitro release of encapsulated pheromone. The microspheres performed best when they were synthesized using an alginate concentration of 4% w/v, at pH = 9 and with a Ca²⁺/COO^? ratio of 3.5. The attractiveness of the alginate/chitosan microspheres towards M. mutatus was demonstrated by behavioral bioassay with the completed pheromonal blend of the species (sulcatol, sulcatone and 3‐pentanol). The formulation can be considered as an efficient slow‐release biological control system, with no negative environmental impact. © 2015 Society of Chemical Industry     

Calcium‐carboxymethyl chitosan hydrogel beads for protein drug delivery system

In this study, carboxymethyl chitosan (CMC) hydrogel beads were prepared by crosslinking with Ca²⁺. The pH‐sensitive characteristics of the beads were investigated by simulating gastrointestinal pH conditions. As a potential protein drug delivery system, the beads were loaded with a model protein (bovine serum albumin, BSA). To improve the entrapment efficiency of BSA, the beads were further coated with a chitosan/CMC polyelectrolyte complex (PEC) membrane by extruding a CMC/BSA solution into a CaCl₂/chitosan gelation medium. Finally, the release studies of BSA‐loaded beads were conducted. We found that, the maximum swelling ratios of the beads at pH 7.4 (17–21) were much higher than those at pH 1.2 (2–2.5). Higher entrapment efficiency (73.2%) was achieved in the chitosan‐coated calcium‐CMC beads, compared with that (44.4%) in the bare calcium‐CMC beads. The PEC membrane limited the BSA release, while the final disintegration of beads at pH 7.4 still leaded to a full BSA release. Therefore, the chitosan‐coated calcium‐CMC hydrogel beads with higher entrapment efficiency and proper protein release properties were a promising protein drug carrier for the site‐specific release in the intestine. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3164–3168, 2007     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis of a novel pH‐sensitive polyurethane–alginate blend with poly(ethylene terephthalate) waste for the oral delivery of protein

With the aim of using poly(ethylene terephthalate) (PET) waste for the synthesis of a value added product, we prepared polyurethane (PU) from bishydrohxyethylene terephthalate (BHET), a byproduct obtained from the glycolysis of PET. Biodegradable, water‐swelling PU was synthesized by the reaction of BHET, hexamethylene diisocyanate, and poly(ethylene glycol) (PEG). Both BHET and PU were characterized by Fourier transform infrared spectroscopy, and the formation of PU was further confirmed by NMR analysis. The swelling behavior of PU in water was examined in terms of the various molecular weights of PEG. Semi‐interpenetrating network beads of PU and sodium alginate were prepared with calcium chloride (CaCl₂) as a crosslinker to attain a pH sensitivity for successful oral protein/drug delivery. Bovine serum albumin (BSA) was used as a model protein. The pH‐responsive swelling behavior and protein (BSA) release kinetics in different pH media corresponding to the gastrointestinal tract (pH 1.2 and 7.4) were investigated. The degree of swelling in the case of the PU–alginate beads at pH 1.2 was found to be at a minimum, whereas the degree of swelling was significantly elevated (1080%) at pH 7.4. This substantiated the pH sensitivity of the polymeric beads with a minimum loss of encapsulated protein in the stomach and the almost complete release of encapsulated protein in the intestine. This revealed good opportunities for oral protein/drug delivery with a polymer derived from waste PET. Moreover, the fungal biodegradation study confirmed its compatibility with the ecological system. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40650.     

Swelling characteristics and in vitro drug release study with pH‐ and thermally sensitive hydrogels based on modified chitosan

The grafting of a poly(ethylene glycol) diacrylate macromer onto a chitosan backbone was carried out with different macromer concentrations. The grafting was achieved by (NH₄)₂Ce(NO₃)₆‐induced free‐radical poly merization. Biodegradable, pH‐ and thermally responsive hydrogels of poly(ethylene glycol)‐g‐chitosan crosslinked with a lower amount of glutaraldehyde were prepared for controlled drug release studies. Both the graft copolymers and the hydrogels were characterized with Fourier transform infrared, elemental analysis, and scanning electron microscopy. The obtained hydrogels were subjected to equilibrium swelling studies at different temperatures (25, 37, and 45°C) in buffer solutions of pHs 2.1 and 7.4 (similar to those of gastric and intestinal fluids, respectively). 5‐Fluorouracil was entrapped in these hydrogels, and equilibrium swelling studies were carried out for the drug‐entrapped gels at pHs 2.1 and 7.4 and 37°C. The in vitro release profile of the drug was established at 37°C and pHs 2.1 and 7.4. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 977–985, 2006     

Temperature sensitive semi‐IPN microspheres from sodium alginate and N‐isopropylacrylamide for controlled release of 5‐fluorouracil

Semi‐interpenetrating network (IPN) of sodium alginate (NaAlg) and N‐isopropylacrylamide (NIPAAm) microspheres were prepared by water‐in‐oil (w/o) emulsification method. The microspheres were encapsulated with 5‐fluorouracil (5‐FU) and release patterns carried in 7.4 pH at temperatures of 25 and 37°C. The semi‐IPN microspheres were characterized by Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry (DSC) and scanning electron microscopic studies were done on the drug‐loaded microspheres to confirm the polymorphism of 5‐FU and surface morphology of microspheres. These results indicated the molecular level dispersion of 5‐FU in the semi‐IPN microspheres. Particle size and size distribution were studied by laser light diffraction technique. Microspheres exhibited release of 5‐FU up to 12 h. The swelling studies were carried in 1.2 and 7.4 pH buffer media at 25 and 37°C. Drug release from NaAlg‐NIPAAm semi‐IPN microspheres at 25 and 37°C confirmed the thermosensitive nature by in vitro dissolution. The micro domains have released in a controlled manner due the presence of NIPAAm in the matrix. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation of poly(ethylene glycol)/chitosan membranes by a glucose‐mediating process and in vitro drug release

Novel pH‐dependent chitosan/poly(ethylene glycol) (PEG) membranes were developed for oral drug delivery. The preparation of these membranes involved a solution‐mediating process with glucose addition at different pHs. Fourier transform infrared/attenuated total reflectance showed that the Schiff‐base reaction was favored at high pHs and high glucose concentrations. X‐ray diffraction analysis showed a continuous increase in the glucose addition transformed the chitosan/PEG samples into amorphous polymers. The equilibrium swelling measurements showed that the swelling ratio of the solution‐mediated membranes decreased as the glucose concentration increased, and this was demonstrated by degree‐of‐mediation analysis. The glucose‐mediated membranes had different degrees of mediation, which depended on the pH and glucose concentration. The in vitro release profiles of theophylline‐loaded, pH 6 treated, glucose‐mediated membranes showed that the theophylline release decreased as the glucose concentration increased. Also, the release behavior of the theophylline from the glucose‐mediated membranes varied with the pH of the release medium, the glucose concentration, and the final pH of the glucose‐mediated chitosan/PEG gels. Chitosan/PEG membranes prepared by a basic glucose‐mediated process could lead to successful applications in localized drug delivery to the intestine. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1083–1094, 2005     

Application of syndiotacticity‐rich PVA hydrogels prepared at a low temperature to thermo‐ and pH‐responsive release devices

Three kinds of physically cross‐linked syndiotacticity‐rich poly(vinyl alcohol) (s‐PVA) hydrogels were prepared at 0°C with use of the buffer solutions (BS) of pHs 4.0, 7.4, and 9.0. Three gels swelled at first and then began to shrink after 12 h when they were dipped in the same BS for preparation at higher temperature than 0°C. The release of Brilliant Blue (3 mg/1 mL) from the cylindrical gels prepared using BS of pH 7.4 was studied at 27, 37, and 47°C. Brilliant Blue has been released spending 4–12 h almost completely. The rate of release from the gel at temperatures of 27, 37, and 47°C became large with increasing temperature. The main factor on release of Brilliant Blue is not the contraction of gel, but swelling, because the degree of swelling (DS) became large with increasing temperatures for 27, 37, and 47°C. The rate of release from the gel (pH 4.0) was larger than that (pH 7.4) due to the increased DS of the hydrogel in early step at pH of 4.0. The apparent diffusion exponents of these releases at pH 7.4 evaluated from first 60% of the fractional release were lower than 0.45 due to the swelling during release. The exponent at pH 4.0 was 0.45 due to immediate swelling. The on‐off of shrinking behavior of atactic PVA (a‐PVA) hydrogel was observed under several temperature changes. The rate of release of Brilliant Blue at 5°C was lower than that at 27°C and no change was observed at 5°C after one on‐off cycle. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 41–46, 2000     

Semiinterpenetrating polymer networks of chitosan and L‐alanine for monitoring the release of chlorpheniramine maleate

In vitro studies have been carried on semiinterpenetrating polymer network (IPN) beads of chitosan–alanine as carrier for the controlled release of chlorpheniramine maleate (CPM) drug. A viscous solution of chitosan–alanine was prepared in 2% acetic acid solution, extruded as droplets by a syringe to NaOH–methanol solution and crosslinked using glutaraldehyde as a crosslinker. The swelling behavior of crosslinked beads in different pH solutions was measured at different time intervals. The swelling behavior was observed to be dependent on pH and degree of crosslinking. The structural and morphological studies of beads were carried out by using a scanning electron microscope. The drug release experiments of different drug loading capacity beads were performed in solutions of pH 2 and pH 7.4 using CPM as a model drug. The concentration of the released drug was evaluated using UV spectrophotometer. The results suggest that chitosan–alanine crosslinked beads are suitable for controlled release of drug. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3751–3757, 2007     

Preparation of porous chitosan/agarose microsphere and its R‐phycoerythrin release properties

The chitosan microspheres (CS‐CL) were prepared by suspension crosslinking method and used as carriers of R‐phycoerythrin (R‐PE). In this study, R‐PE was loaded in the microspheres and released in vitro. The effects of pH value, temperature, ionic strength, and R‐PE concentration on loading efficiency and release behavior were discussed. A novel microsphere that contained agarose (CS‐AR MP) was prepared and the basic loading and releasing behavior for R‐PE of this kind of new microspheres were also investigated. The results showed that all these chitosan microspheres have the ability to control‐release R‐PE. The addition of agarose may somewhat accelerate the release rate of R‐PE from microspheres and reduce the capacity of adsorption for R‐PE. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2759–2766, 2007     

Production of polycaprolactone–polyethylene glycol–sodium alginate biocomposites for spray drying encapsulation of <Emphasis Type="SmallCaps">l</Emphasis>-ascorbic acid

l-Ascorbic acid was encapsulated in biopolymers to enhance (1) its encapsulation efficiency and (2) drug release ratio using different pH media. To achieve this goal, we used polycaprolactone (PCL), polyethylene glycol (PEG), and sodium alginate (SA) to prepare drug delivery system and spray dryer as our tool to obtain microspheres. In this manner, the importance of the study was to produce a stable and effective drug encapsulation system by PCL–PEG–SA polymer mixture by spray dryer. First we evaluated the effects of drying conditions and composition on the microencapsulation formulation and in the next stage the most uniformly distributed particles were selected and l-ascorbic acid was loaded. After that, drug encapsulation and drug release studies were performed. Drug release experiments were conducted at different pH solutions (pH 2.5, 7.4, and 9.6). Finally, drug release kinetics was determined by widely used equations to describe the degradation kinetics; zero-order, first-order, Higuchi, Hixson–Crowell, and Korsmeyer–Peppas. Furthermore, l-ascorbic acid release mechanism from microspheres was also determined. The release profiles of three microspheres obeyed the earlier developed kinetic models for performing possible release mechanisms. The Korsmeyer–Peppas model best described each release scenario.     

Facile and green preparation of thermal and ph sensitive hydrogel microspheres based on spray drying and the diels–alder reaction

Thermal and pH dual‐sensitive hydrogel microspheres were fabricated using spray drying. During the spray drying, chemical crosslinks were formed in situ via the Diels–Alder reaction without the involvement of any catalysts or organic solvents. The structures and morphologies of the products were characterized by Fourier Transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), Raman spectroscopy, scanning electron microscopy (SEM), X‐ray diffraction (XRD), and thermogravimetric analysis (TGA). A general weighing method was applied to study the swelling behavior of the microspheres at different temperatures and pHs. Using urea as a model molecule, the ability of the microspheres to control the release of urea was explored by spectrophotometry and calculated from the calibration curve obtained from the reaction of urea and diaminobenzaldehyde. The as‐prepared microspheres show a reversible and reproducible volume change with varying pH or temperature, and their swelling ratios increase with increasing temperature or pH. Furthermore, the urea release rates can be tuned by changing the pH or the temperature. Since spray drying can easily produce microspheres on a large scale, the strategy demonstrated here has the potential for applications in the green preparation of hydrogel microspheres. POLYM. ENG. SCI., 59:1999–2007, 2019. © 2019 Society of Plastics Engineers     

Chitosan/polyethylene glycol–alginate microcapsules for oral delivery of hirudin

A mild chitosan/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as albumin and hirudin, was investigated. The polysaccharide chitosan was reacted with sodium alginate in the presence of calcium chloride to form microcapsules with a polyelectrolyte complex membrane. Hirudin-entrapped alginate beads were further surface coated with polyethylene glycol (PEG) via glutaraldehyde functionalities. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within the initial 6 h and about 35% release of hirudin was also observed during treatment with 0.1 M HCl, pH 1.2 for 4 h. But acid-treated capsules had released almost all the entrapped hirudin into Tris-HCl, pH 7.4 media within 6 h. From scanning electron microscopic and swelling studies, it appears that the chitosan and PEG have modified the alginate microcapsules and subsequently the protein release. The microcapsules were also prepared by adding dropwise albumin-containing sodium alginate mixture into a PEG– CaCl₂ system. Increasing the PEG concentration resulted in a decrease rate of albumin release. The results indicate the possibility of modifying the formulation to obtain the desired controlled release of bioactive peptides (hirudin), for a convenient gastrointestinal tract delivery system. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 70: 2143–2153, 1998     

快速膜乳化与热固化法制备粒径均一的pH敏感壳聚糖季铵盐凝胶微球

以具有升温自固化特性的壳聚糖季铵盐/甘油磷酸钠混合溶液为水相,利用快速膜乳化与热固化法制备了粒径均一、pH敏感的壳聚糖季铵盐凝胶微球,考察了跨膜压力、水油相组成、水油相体积比及微孔膜孔径等对微球粒径、结构和药物包埋率的影响. 结果表明,得到粒径698±57.33, 1145±71.48, 2021±53.63及3984±191.72 nm、粒径分布窄(多分散系数<0.1)、药物包埋率高达75.49%±2.62%的凝胶微球. 所制微球生物相容性好,有明显的pH敏感性,中性和碱性环境下结构稳定,药物缓释,pH=7.4时24 h内药物累计释放率为34.6%;酸性环境下微球崩解,药物快速释放,pH=5.5时1 h内药物累计释放率高达79.6%.     

复相乳化法制备海藻酸钙微球及其释放行为

采用复相乳化法制备了载牛血清白蛋白(BSA)的海藻酸钙微球,通过正交实验和单因素分析,以BSA包埋率、微球的载药率和平均粒径为考察指标,优化了该方法的制备参数,使最终制备的微球平均粒径小于10 mm,球形度较好,包埋率约70%,载药率达4%. 随着海藻酸钠质量分数的降低和BSA质量的增大,微球的包埋率下降、载药率升高、平均粒径减小. 微囊化BSA的体外释放曲线表明,该系统存在pH响应特性,尤其在磷酸缓冲液中,被包埋BSA的释放速率较快. 电泳结果表明,BSA的分子结构并未受制备过程的影响. 因此,该微囊化方法有望用于蛋白类药物的控释制剂,使其免受胃酸等的破坏,达到肠部释药的目的.     

Dual crosslinked carboxymethyl sago pulp/pectin hydrogel beads as potential carrier for colon‐targeted drug delivery

Carboxymethyl sago pulp (CMSP)/pectin hydrogel beads were synthesized by calcium crosslinking and further crosslinked by electron beam irradiation to form drug carrier for colon‐targeted drug. Sphere‐shaped CMSP/pectin 15%/5% hydrogel beads is able to stay intact for 24 h in swelling medium at pH 7.4. It shows pH‐sensitive behavior as the swelling degree increases as pH increases. Fourier transform infrared spectroscopy analysis confirmed the absence of chemical interaction between hydrogel beads and diclofenac sodium. Differential scanning calorimetric and X‐ray diffraction studies indicate the amorphous nature of entrapped diclofenac sodium. The drug encapsulation efficiency is up to about 50%. Less than 9% of drug has been released at pH 1.2 and the hydrogel beads sustain the drug release at pH 7.4 over 30 h. This shows the potential of CMSP/pectin hydrogel beads as carrier for colon‐targeted drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43416.     

Beta cyclodextrin–insulin‐encapsulated chitosan/alginate matrix: Oral delivery system

Cyclodextrins (CD) form inclusion complexes with many drug molecules. The complexed drugs have increased bioabsorption in in vivo system. We have attempted to complex insulin with β‐Cyclodextrin (BCD) and encapsulate in the chitosan/calcium alginate matrix. For drug release studies insulin complexed with BCD for 20 min and that complexed with BCD for 150 min have been used for encapsulation in the chitosan/calcium alginate matrix. The two matrices seem to have different drug release profiles in simulated intestinal medium (pH 7.4) It appears that drug release from the 20‐min BCD complexed system encapsulated in the chitosan/calcium alginate matrix begins only after an hour, where, being released from the 150‐min BCD complexed system it begins in the first hour itself. Also, aggregation of the insulin molecules seems to be reduced by the complexation of the drug with BCD. Another noticeable fact is the change in the loading character, which is found to be inversely related to the concentration of BCD when it is above the stoichiometric equivalent of the drug. In an attempt to increase the payload of the drug in the matrix, the pH of the processing medium consisting of calcium chloride and chitosan is varied. It is found that the encapsulation efficiency increases as the pH is decreased from 6.0 to 4.0. Another way of increasing the loading is studied by decreasing the concentration gradient of insulin in the processing alginate solution and the crosslinking medium consisting of chitosan/calcium chloride. Preliminary animal studies on rabbits seem to be promising. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 1089–1096, 2000