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     

Preparation and in vitro evaluation of new pH‐sensitive hydrogel beads for oral delivery of protein drugs

New biodegradable pH‐responsive hydrogel beads based on chemically modified chitosan and sodium alginate were prepared and characterized for the controlled release study of protein drugs in the small intestine. The ionotropic gelation reaction was carried out under mild aqueous conditions, which should be appropriate for the retention of the biological activity of an uploaded protein drug. The equilibrium swelling studies were carried out for the hydrogel beads at 37°C in simulated gastric (SGF) and simulated intestinal (SIF) fluids. Bovine serum albumin (BSA), a model for protein drugs was entrapped in the hydrogels and the in vitro drug release profiles were established at 37°C in SGF and SIF. The preliminary investigation of the hydrogel beads prepared in this study showed high entrapment efficiency (up to 97%) and promising release profiles of BSA. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and evaluation of chitosan‐coated polyphosphazene hydrogel beads for drug controlled release

Chitosan‐coated polyphosphazene‐Ca²⁺ hydrogel beads were fabricated by dropping polyphosphazene into CaCl₂/chitosan gelling solution. Polyphosphazene used here was a water‐soluble degradable polyanion (PCPAP), which carried almost two carboxylatophenamino groups on each phosphorus atom of the polymer backbone. Two kinds of turbidimetric titration were applied in this study to reveal the interaction between PCPAP and chitosan within the pH range of 4.57≈7.14. The effect of gelling solution pH on the properties of chitosan‐coated PCPAP beads was especially emphasized. It was found that the PCPAP/chitosan complex prepared at relatively high pH (pH 6.5) dissociated most slowly in pH 7.4 phosphate‐buffered solution (PBS). The erosion of chitosan‐coated beads and the release of model drug (Coomassie brilliant blue and myoglobin) in PBS were both obviously prolonged with the increase of gelling solution pH, exhibiting perfect accordance with the behavior of complex dissociation. In addition, the coating of PCPAP/chitosan complex on the bead surface facilitated the improvement of drug loading efficiency. The higher the gelling solution pH, the more the drug loading efficiency improved. At pH 6.5 (PCPAP 5%, CaCl₂ 7%, chitosan 0.3%), the loading efficiency of myoglobin in beads reached as high as 93.2%. These results indicate that the chitosan‐coated polyphosphazene‐ Ca²⁺ bead is a potential formulation for drug controlled release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1993–1999, 2004     

Preparation and release behavior of carboxymethylated chitosan/alginate microspheres encapsulating bovine serum albumin

Microspheres were prepared from carboxymethylated chitosan (CM‐chitosan) and alginate by emulsion phase separation. Their structure and morphology were characterized with IR spectroscopy and scanning electron microscopy. Bovine serum albumin (BSA) was encapsulated in the microspheres to test the release behavior. The swelling behavior, encapsulation efficiency, and release behavior of BSA from the microspheres at different pHs and with a pH‐gradient condition were investigated. The BSA encapsulation efficiency was calculated to be 80%. The degree of swelling of the microspheres without BSA loaded at pH 7.2 was much higher than that at pH 1.0. The encapsulated BSA was quickly released in a Tris–HCl buffer (pH 7.2), whereas a small amount of BSA was released under acid conditions (pH 1.0) because of the strong electrostatic interaction between ? NH₂ groups of CM‐chitosan and ? COOH groups of alginic acid and a dense structure caused by a Ca²⁺ crosslinked bridge. For the simulation of the processing of the drug under the conditions of the intestine, the microspheres were tested in a pH‐gradient medium, in which an acceleration of the release occurred at pH 7.4 after a lag time at a low pH (5.8–6.8). At pH 7.4, a large amount of BSA was released from the microspheres in a short time because of the rapid swelling of the microspheres. However, the release only depended on the diffusion of BSA at relatively low pHs, this resulted in a relatively low release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 878–882, 2004     

Preparation and characterization of venlafaxine hydrochloride‐loaded chitosan nanoparticles and in vitro release of drug

The venlafaxine hydrochloride (VHL)‐loaded chitosan nanoparticles were prepared by ionic gelation of chitosan (CS) using tripolyphosphate (TPP). The nanoparticles were characterized using FTIR, differential scanning calorimetry, X‐ray diffraction, dynamic light scattering, transmission electron microscopy, and X‐ray photoelectron spectroscopy. The effect of concentration of CS, polyethylene glycol (PEG), VHL and CS/TPP mass ratio on the particle size and zeta potential of nanoparticles was examined. The particle size of CS/TPP nanoparticles and VHL‐loaded CS/TPP nanoparticles was within the range of 200–400 nm with positive surface charge. In the case of VHL‐loaded nanoparticles and PEG‐coated CS/TPP nanoparticles, the particle size increases and surface charge decreases with increasing concentration of VHL and PEG. Both placebo and VHL‐loaded CS/TPP nanoparticles were observed to be spherical in nature. PEG coating on the surface of CS/TPP nanoparticles was confirmed by XPS analysis. Maximum drug entrapment efficiency (70%) was observed at 0.6 mg/mL drug concentration. In vitro drug release study at 37°C ± 0.5°C and pH 7.4 exhibited initial burst release followed by a steady release. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation,evaluation, and in vitro release study of O‐carboxymethyl chitosan nanoparticles loaded with gentamicin and salicylic acid

To inhibit the ototoxicity of gentamicin (GM) and overcome the drawback related to chitosan (CS) nanoparticles preparation in acid solution, O‐carboxymethyl chitosan (O‐CMC) nanoparticles loaded with GM and salicylic acid (SA) were prepared by ionic cross‐linking method using calcium chloride as crosslinking agent. The Fourier transform infrared (FTIR) spectroscopy and X‐ray diffraction (XRD) were used to analyze the reaction of O‐CMC and crosslinking agent. The parameters of preparation of the compound nanoparticles including the concentration of O‐CMC, the mass ratio of O‐CMC to calcium chloride, and the feed ratio of SA to GM were investigated. The results showed that the obtained nanoparticles had a high zeta potential and drug‐loading capacity. The nanoparticles were characterized by a spherical morphology, with average size ranging from 148 to 345 nm and a narrow particle size distribution. In vitro release studies in phosphate buffer saline (pH 7.4) evidenced a burst release in the first 1 h, followed by a sustained release in the residual time. The release amount of SA and GM were approximately equal in 24 h, which indicated that the SA‐ and GM‐loaded O‐CMC nanoparticles are a promising carrier system for inhibiting the ototoxicity of GM. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

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.     

Alginate/BSA/montmorillonite composites with enhanced protein entrapment and controlled release efficiency

Novel pH sensitive alginate–protein–clay composite beads were investigated for the in vitro oral delivery of the model protein, bovine serum albumin (BSA). X-ray diffraction (XRD) results revealed that BSA enter between layers of montmorillonite (MMT) by expanding interlayer distance and finally an exfoliated structure forms in the alginate hydrogel. MMT incorporation increases protein entrapment efficiency to 78%, compared to 40% of conventional alginate beads. The release ratio of BSA from composite beads is 9–13% depending on MMT contents after around a 2 h stay in gastric fluid. More importantly, no BSA release is detected until 60–90 min after the first contact time of beads with gastric solution. The presence of clay in alginate beads prevents burst release in higher pH of intestine by slowing release rate of BSA to 45–55% within around 9 h, resulting in a potential matrix for intestinal release of protein drugs.     

Controlled release of berberine hydrochloride from alginate microspheres embedded within carboxymethyl chitosan hydrogels

Berberine hydrochloride is a natural medicine with wide clinical application. In this article, berberine hydrochloride was entrapped into alginate microspheres via an emulsification/gelation method. The size distribution of the microspheres was determined by a laser particle sizer. Drug distribution within the microspheres was determined by confocal laser scanning microscopy. Those drug‐loaded microspheres were further entrapped into carboxymethyl chitosan (CMC) hydrogel to form a new drug‐delivery system (DDS). The surface morphology of the DDS was observed using metallographic microscopy and scanning electron microscopy (SEM). The compression strength of the DDSs with alginate microspheres was found significantly higher than that of the pure hydrogel. The drug‐release performances of the DDS in phosphate buffer solution (PBS, pH 7.4), saline solution (pH 6.3), and hydrochloric acid solution (HAS, pH 1.2) were also studied. Decay of the DDS in PBS within 72–80 h results in a faster release; however, the steady release in saline solution could last for all the testing period without cleavage of the DDS. In HAS, because of the shrinkage of the DDS, release is fast in the first period and remains steady later. The DDS exhibits prospective in controlled steady release of drugs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Investigation on the development of sturdy bioactive hydrogel beads

Biocatalytic hydrogel beads, which retain higher activity, expand, and contract with changes in pH, having biocompatibility, are developed. Composite spherical beads of chitosan having a diameter of 1–2 mm were prepared by ionic gelation using sodium tripolyphosphate (TPP). Above 3% TPP, the activity of the enzyme decreases. The mechanical strength of the chitosan–TPP beads was further improved by the addition of clay or cassava starch granules. The immobilization of protease (fungal, Aspergillus) was done with glutaraldehyde crosslinking. The chitosan–starch hydrogel beads showed significant increase in firmness and stiffness when compared with chitosan–clay beads. The swelling studies show that the particles expand at pH 1.2 and contract at pH 7.4. The activity retention of the immobilized protease was as high as 70% and exhibited a high pH and lower temperature optima than the free enzyme. Chitosan–starch hydrogel beads exhibited degradation peaks at about 90–110°C in TGA analysis. The biocatalyst beads retained 85% of the original catalytic activity even after eight cycles of repeat use. The freeze‐dried beads has good storage stability and can be used either as artificial bioreactor systems in detergent or in therapeutic formulations © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

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     

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     

Comparison of poly(aspartic acid) hydrogel and poly(aspartic acid)/gelatin complex for entrapment and pH‐sensitive release of protein drugs

Biodegradable poly(aspartic acid) (PASP) hydrogel and PASP/gelatin complex were prepared to evaluate their potential application as pH‐sensitive matrices for controlled protein release. Entrapment of myoglobin (Mb) and its release were compared between the two types of carriers. It was found that incorporation of Mb into PASP hydrogel strongly depended on the medium pH and NaCl concentration, and was time‐consuming. However, complete entrapment of Mb into PASP/gelatin complex was found within pH ranged from 2.5 to 4.0, which was concomitant with the formation of PASP/gelatin complex. By adjusting Mb feed ratio, Mb entrapment in the complex can be up to 31.54% (by weight) with high loading efficiency (96.2%). Gradual release of Mb from PASP hydrogel was observed within pH 2.0–7.4, while Mb release from PASP/gelatin complex was negligible within pH 2.0–4.2 for 4 days. In addition, pulsatile Mb release can be achieved by combining polyanhydride with pH‐sensitive PASP/gelatin complex, while the device composed of polyanhydride and PASP hydrogel is mechanically unstable. PASP/gelatin complex formed by electrostatic interactions is superior to the single‐component PASP hydrogel synthesized by chemical cross‐linking as pH‐sensitive matrices for controlled protein release when entrapment of proteins and pH‐sensitivity of protein release are concerned. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Electrospray preparation of propranolol‐loaded alginate beads: Effect of matrix reinforcement on loading and release profile

In the present study, propranolol loaded‐calcium alginate beads were prepared from concentrated solutions of sodium alginate, using combined method of electrospray and ionotropic gelation. The objectives of the study were to increase the propranolol‐HCl loading and to decrease its initial burst release. However, the effects of voltage, nozzle diameter, flow rate, and concentration of sodium alginate on size of the beads and drug entrapment efficiency (DEE) were also investigated. The matrix of alginate beads was reinforced with dextran sulfate and/or coated with chitosan. The mean particle size of the beads, their swelling behavior, and drug entrapment efficiency were characterized. Furthermore, the drug release profiles from the prepared beads in simulated gastric fluid and intestinal fluid were evaluated and compared. Among the parameters that affected the electrospray of alginate, voltage had a pronounced effect on the size of beads. The size of beads was reduced to a minimum value on increasing the voltage. Furthermore, increasing the flow rate, alginate concentration, and nozzle diameter and decreasing the voltage led to improvement in DEE. Enhancing the alginate concentration as well as coating with chitosan and reinforcing with dextran sulfate led to increase of the encapsulation efficiency and therefore decrease of the drug release rate in both pHs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41334.     

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.     

Properties of chitosan/poly(vinyl alcohol) films for drug‐controlled release

With bovine serum albumin (BSA) as a model drug, drug‐loaded films of chitosan (CS) and poly(vinyl alcohol) (PVA) were obtained by a casting/solvent evaporation method and crosslinked by tripolyphosphate (TPP). The films were characterized by FTIR, XRD, and SEM. The influential factors of drug‐loaded films on drug‐controlled release were studied. These factors included, primarily, the component ratio of CS and PVA, the loaded amount of BSA, the pH and ionic strength of the release solution, and the crosslinking time with TPP. The results showed that within 25 h, when the weight ratios of CS to PVA in the drug‐loaded films were 90 : 10, 70 : 30, 50 : 50, and 30 : 50, the cumulative release rates of BSA were 63.3, 72.9, 81.8, and 91.8%, respectively; when the amounts of model drug were 0.1, 0.2, and 0.3 g, the release rates were 100, 81.8, and 59.6%, respectively; when the pH values of the drug release medium were 1.0, 3.8, 5.4, and 7.4, the release rates reached 100, 100, 37.9, and 7.8%, respectively; the cumulative release rates of BSA were 78.4, 82.3, 84.3, and 91.7% when the ionic strengths of the release solution were, respectively, 0.1, 0.2, 0.3, and 0.4M; when the crosslinking times of these drug films in the TPP solution were 0, 5, 15, 30, and 60 min, the release rates attained 100, 100, 81.8, 65, and 43.3%, respectively. All the results indicated that the CS/PVA film was useful in drug delivery systems. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 808–813, 2005     

Antibacterial activity of chitosan–alginate sponges incorporating silver sulfadiazine: Effect of ladder‐loop transition of interpolyelectrolyte complex and ionic crosslinking on the antibiotic release

Hydrogel membranes prepared from polyelectrolyte complex (PEC) have been used for repair of wounds and controlled antibacterial release. A simple method, based on homogenizing interpolyelectrolyte complex, has been developed to prepare a chitosan–alginate sponge with high stability. The spongelike chitosan–alginate hydrogel can be used as a wound dressing for the sustained release of silver sulfadiazine (AgSD) in a controlled way. In this study, we evaluated the effect of electrolyteic properties of chitosan and alginate on the characteristics of the prepared chitosan–alginate PEC. All types of the spongelike chitosan–alginate hydrogels exhibited superabsorbent properties. However, only the chitosan–alginate hydrogel prepared by the interpolyelectrolyte complex of alginate with low pH of chitosan, and that prepared by the interpolyelectrolyte complex of chitosan with high pH of alginate, can keep their stability after swelling in PBS solution. FTIR analysis suggests that the protonated amino groups on chitosan and the ionized carboxylic groups on alginate should be responsible for the formation of a stable ladder‐type of chitosan–alginate PEC. Ionic crosslinking is helpful to increase the stability of the loop‐type of chitosan–alginate PEC. The release of AgSD from chitosan–alginate PEC sponges could be controlled by the variation of ladder‐loop structural transition of chitosan–alginate PEC and the ionic crosslinking of the chitosan–alginate complex. The antibacterial ability of AgSD‐incorporated PEC sponges was examined in agar plate against Pseudomonas aeruginosa and Staphylococcus aureus. The result suggests that the PEC sponges containing antimicrobial agents should effectively suppress bacterial proliferation to protect the wound from bacterial invasion. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 538–549, 2005     

pH-sensitive hydrogel based on carboxymethyl chitosan/sodium alginate and its application for drug delivery

Carboxymethyl chitosan sodium salt (CMCS)/sodium alginate (SA), a pH-sensitive hydrogel composed of CMCS and SA crosslinked by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide, has been evaluated in vitro as a potential carrier for protein drug delivery of bovine serum albumin (BSA). The crosslinked structures, pore morphologies, and mechanical properties of the composite CMCS/SA hydrogel at different pH have been characterized by Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and dynamic mechanical analysis (DMA). The swelling behavior of the prepared hydrogel was assessed at different pH values, 1.2, 4.0, 6.86, 7.4, and 9.0. The in vitro slow release ability of the CMCS/SA hydrogel was assessed at 37°C and pH 1.2 or pH 7.4 to simulate gastrointestinal and mouth environments in vivo. The efficiency was found to be greater than 90% at pH 7.4. The composite CMCS/SA hydrogel showed no cytotoxic effect toward L-929 cells according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. These findings demonstrate that the composite hydrogel has promising potential for drug delivery. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46911.     

Chitosan–polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. II. Effect of pH‐dependent ionic crosslinking or interpolymer complex using tripolyphosphate or polyphosphate as reagent

Chitosangel beads were prepared using an in‐liquid curing method by ionotropic crosslinking or interpolymer linkage with tripolyphosphate (TPP) or polyphosphate (PP). The ionic interaction of chitosan with TPP or PP is pH‐dependent due to the transition of “ladder‐loop” complex structures. Chitosan gel beads cured in a pH value lower than 6 of a TPP solution was a controlled homogeneous ionic‐crosslinking reaction, whereas chitosan gel beads cured in a lower pH PP solution was a nonhomogeneous interpolymer complex reaction due to the mass‐transfer resistance for the diffusion of macromolecular PP. According to the results of FTIR and EDS studies, it was suggested that significantly increasing the ionic‐crosslinking density or interpolymer linkage of a chitosan–TPP or chitosan–PP complex could be achieved by transferring the pH value of curing agent, TPP or PP, from basic to acidic. The swelling behavior of various chitosan beads in acid medium appeared to depend on the ionic‐crosslinking density or interpolymer linkage of the chitosan–TPP or chitosan–PP complex, which were deeply affected by the in‐liquid curing mechanism of the chitosan gel beads. By the transition of the in‐liquid curing mechanism, the swelling degree of chitosan–TPP or chitosan–PP beads was depressed and the disintegration of chitosan–TPP or chitosan–PP beads did not occur in strong acid. The drug‐release patterns of the modified chitosan gel beads in simulated intestinal and gastric juices were sustained for 20 h. These results indicate that the sustained release of anticancer drugs could be achieved due to the variation of the reaction mechanism of a chitosan–polyelectrolyte pH‐dependent ionic interaction. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 1093–1107, 1999     

Semi‐interpenetrating polymer network beads of crosslinked chitosan–glycine for controlled release of chlorphenramine maleate

Spherical, semi‐interpenetrating polymer network beads of chitosan and glycine, crosslinked with different concentrations of glutaraldehyde were prepared for controlled release of drugs. The structural and morphological studies of the beads were carried out with FTIR and SEM techniques. The swelling behavior of the beads at different time intervals was monitored in solutions of different pH. Structural changes of the beads in response to solution pH were put forward using the data obtained from IR/UV spectral analysis. The release experiments were performed in solutions of pH 2.0 and pH 7.4 at 37°C, using chlorphenramine maleate as a model drug. The results indicate that, chitosan might be useful as a vehicle for controlled release of drugs. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 672–683, 2000