Kinetic study of chitosan‐tripolyphosphate complex reaction and acid‐resistive properties of the chitosan‐tripolyphosphate gel beads prepared by in‐liquid curing method

Chitosan gel beads were prepared using an in‐liquid curing method by the ionotropic crosslinking with sodium tripolyphosphate. Crosslinking characteristics of the chitosan‐TPP beads were improved by the modification of in‐liquid curing mechanism of the beads in TPP solution. Chitosan gel beads cured in pH value lower than 6 were really ionic‐crosslinking controlled, whereas chitosan gel beads cured in pH values higher than 7 were coacervation‐phase inversion controlled accompanied with slightly ionic‐crosslinking dependence. According to the result, significantly increasing the ionic‐crosslinking density of chitosan beads could be achieved by transferring the pH value of the curing agent, TPP, from basic to acidic. The swelling behavior of various chitosan beads in acid appeared to depend on the ionic‐crosslinking density of the chitosan‐TPP beads that were deeply affected by the curing mechanism of the beads. The mechanism of chitosan‐TPP beads swollen in weak acid was chain‐relaxation controlled, while the mechanism of chitosan‐TPP beads swollen in strong acid seem to be not only chain‐relaxation but also chain‐scission controlled. Chitosan‐TPP beads prepared in acidic TPP solution decreased the chain‐scission ability due to the increase of ionic crosslinking density of the beads. By the transition of curing mechanism, the swelling degree of chitosan‐TPP beads was depressed, and the disintegration of chitosan‐TPP beads would not occur in strong acid. The mechanism of ionic‐crosslinking reaction of chitosan beads could be investigated by an unreacted core model, and the curing mechanism of the chitosan beads is mainly diffusion controlled when higher than 5% of chitosan was employed. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1551–1564, 1999     

Dual crosslinked pH‐ and temperature‐sensitive hydrogel beads for intestine‐targeted controlled release

Novel drug‐loaded hydrogel beads for intestine‐targeted controlled release were developed by using pH‐ and temperature‐sensitive carboxymethyl chitosan‐graft‐poly(N,N‐diethylacrylamide) (CMCTS‐g‐PDEA) hydrogel as carriers and vitamin B₂ (VB₂) as a model drug. The hydrogel beads were prepared based on Ca²⁺ ionic crosslinking in acidic solution and formed dual crosslinked network structure. The structure of hydrogel and morphology of drug‐loaded beads were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The study about swelling characteristics of hydrogel beads indicated that the beads had obvious pH‐ and temperature‐sensitivity. In vitro release studies of drug‐loaded beads were carried out in pH 1.2 HCl buffer solution and pH 7.4 phosphate buffer solution at 37°C, respectively. The results indicated that the dual crosslinked method could effectively control the drug release rate under gastrointestinal tract (GIT) conditions, which was superior to traditional single crosslinked beads. In addition, the effects of grafting percentage, pH value, and temperature on the release behavior of the VB₂ were investigated. The drug release mechanism of CMCTS‐g‐PDEA drug‐loaded beads was analyzed by Peppa's potential equation. According to this study, the dual crosslinked hydrogel beads based on CMCTS‐g‐PDEA could serve as suitable candidate for drug site‐specific carrier in intestine. Copyright © 2009 John Wiley & Sons, Ltd.     

Studies in the development of nateglinide loaded calcium alginate and chitosan coated calcium alginate beads

Nateglinide loaded alginate-chitosan beads were prepared by ionic gelation method for controlling the drug release by using various combinations of chitosan and Ca2+ as cation and alginate as anion. IR spectrometry, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry were used to investigate the physicochemical characteristics of the drug in the bead formulations. The calcium content in beads was determined by atomic absorption spectroscopy. The swelling ability of the beads in different media (pH 1.2, 4.5, 6.8) has been found to be dependent on the presence of polyelectrolyte complex of the beads and the pH of the media. The ability to release the Nateglinide was examined as a function of chitosan and calcium chloride content in the gelation medium. It is evident that the rate of drug release and its kinetics could be controlled by changing the chitosan and the calcium chloride concentrations. Calcium alginate beads released more than 95% of drug with in 8 h; whereas coated beads sustained the drug release and released only 75-80% of drug. The drug release mechanism analyzed indicates that the release follows either "anomalous transport" or "case-II transport".     

Sorption behaviour of fluoride on carboxylated cross-linked chitosan beads

Carboxylated cross-linked chitosan beads (CCB) showed a significant defluoridation capacity (DC) of 1385 mgF(-)/kg than the raw chitosan beads (CB) which displayed only 52 mgF(-)/kg. Sorption experiments were performed by varying contact time, pH, presence of co-anions and temperature. The nature and morphology of the sorbent were discussed using FTIR and SEM with EDAX analysis. The stability of the beads in solution was explained in terms of swelling ratio of the beads. The fluoride uptake onto CCB obeys both Freundlich and Langmuir isotherms. Thermodynamic studies revealed that the nature of fluoride sorption is spontaneous and endothermic. Sorption kinetics is mainly controlled by pseudo-second-order and intraparticle diffusion models. 0.1M HCl was identified as the best eluent. The suitability of CCB at field conditions has been tested with field sample collected from a nearby fluoride-endemic area.     

壳聚糖-聚丙烯酸复合水凝胶的药物控制释放行为

以壳聚糖(Cs)和丙烯酸(AA)为原料,利用自由基聚合法制备了具有孔洞结构的复合水凝胶Cs-PAA,并研究了AA的量、交联剂的量、聚合温度和AA的中和度对水凝胶溶胀度的影响以及复合水凝胶对烟酸的控制释放。 结果表明,Cs-PAA复合水凝胶具有良好的pH值、离子强度敏感性,且溶胀度最高达1228 g/g,其在pH=686的缓冲溶液中的烟酸累积释放率明显大于其在pH=1.80的缓冲溶液,因此Cs-PAA水凝胶可作为肠口服药物的载体。     

Effect of molecular weight and degree of deacetylation on controlled release of isoniazid from chitosan microspheres

Glutaraldehyde cross‐linked chitosan microspheres for controlled release of isoniazid were prepared using chitosan of different molecular weights (MWs) and degrees of deacetylation (DDAs). Chitosan microspheres were characterized for their size, hydrophobocity, degree of swelling and loading of isoniazid. Hydrophobicity of chitosan microspheres increased on increasing the degree of cross‐linking and MW of chitosan. Chitosan microspheres with high degree of deacetylation (DDA) (75 wt%), high MW chitosan (2227 kg mol^?1), and with 12 wt% concentration of glutaraldehyde showed optimum loading and release of isoniazid. The isoniazid from chitosan microspheres was released in two steps, i.e. burst (%R_B) and controlled (%R_C) steps. The microspheres with low MW chitosan (260 kg mol^?1) and low DDA (48 wt%) showed prominent burst release of isoniazid, but microspheres with high MW chitosan (2227 kg mol^?1) and high DDA (75 wt%) have released more isoniazid in a controlled manner (60 wt%) at 37°C in a solution of pH 5.0 ± 0.1. The burst step of drug release (%R_B) has followed first order kinetics, whereas controlled step of drug release (%R_C) followed zero order kinetics. The burst step of drug release was Fickian and controlled step was non‐Fickian in nature. The diffusion constant (D) for isoniazid release was influenced by the properties of chitosan and degree of cross‐linking. Copyright © 2007 John Wiley & Sons, Ltd.     

Radiation grafting of ionically crosslinked alginate/chitosan beads with acrylic acid for lead sorption

Radiation-induced grafting of acrylic acid onto alginate/chitosan beads was performed in solution at a dose rate of 20.6 Gy/min of Co-60 gamma rays. The effect of absorbed dose on grafting yield was investigated. The characterization of the grafted and un-grafted beads was performed by FTIR spectroscopy and the swelling measurements at different pHs was studied. It is found that as the pH value increases the swelling degree increases up to pH 6 but with further increase in pH value the swelling decreases. Also, it is noticed that the grafting yield increased with increase the irradiation dose. Both un-grafted and grafted alginate/chitosan beads were examined as sorbents for the removal of Pb ions from aqueous solutions. The sorption behavior of the sorbents was examined through pH, and equilibrium measurements. Grafted alginate/chitosan beads presented higher sorption capacity for Pb ions than un-grafted beads.     

Biodegradable biocompatible xyloglucan films for various applications

Polysaccharides are known for their film-forming properties which have been intensively investigated for food and non-food applications. Here we have developed a xyloglucan transparent film for various applications especially in controlled release of drugs and cosmetics. The present study evaluated the properties of the composite films of xyloglucan, chitosan and rice starch obtained by the casting/solvent evaporation method. Xyloglucan chitosan blend film shows better mechanical properties. Hydrophobicity and crystallinity of xyloglucan film was increased by blending with chitosan. This was confirmed by X-ray diffraction studies and contact angle measurements. Scanning electron microscopic observations indicated that the xyloglucan chitosan blend films were smooth and homogenous. Thermogravimetric and differential scannining calorimetric analysis showed a high thermal stability and melting temperature of xyloglucan chitosan film compared with others. The swelling properties of the xyloglucan chitosan blend film, studied as a function of pH showed that the sorption ability of the blend film was high at a pH 7.4. This indicates its controlled release property at that pH. Controlled drug release property of the film was studied by using streptomycin as a model drug.     

STRUCTURAL CHANGES AND RELEASE CHARACTERISTICS OF CROSSLINKED CHITOSAN BEADS IN RESPONSE TO SOLUTION pH

The present investigation describes a novel method for preparing beads based on crosslinked chitosan with glutaraldehyde interpenetrating glycine polymer network. Four type of beads, viz., CHI1 (composed of chitosan, glycine and glutaraldehyde); CHI2 (composed of chitosan and glutaraldehyde); CHI3 (composed of chitosan and glycine) and CHI4 (only chitosan) were prepared and their release characteristics were studied using thyamine hydrochloride (Thy-HCl) as a model drug. Structural changes during swelling of CHI1 beads in solutions of different pH were studied using IR and UV spectroscopy.     

Formulation characterization and in vitro evaluation of acacia gum–calcium alginate beads for oral drug delivery systems

In the present work, new matrix bead formulations based on linear and branched polysaccharides have been developed using an ionic gelation technique, and their potential use as oral drug carriers has been evaluated. Using calcium chloride as a cross‐linking agent and sodium diclofenac (SD), as a model drug, acacia gum–calcium alginate matrix beads were formulated. The response surface methodology based on 3² factorial design was used as a statistical method to evaluate and optimize the effects of the biopolymers‐blend ratio and the concentration of calcium chloride on the particle size (mm), density (g/cm³), drug encapsulation efficiency (%), and the cumulative drug release after 8 hours (R_8h,%). The optimized beads with the highest drug encapsulation efficiency were examined for a drug‐excipients compatibility by powder X‐ray diffraction, differential scanning calorimetry, thermo‐gravimetric analysis, and Fourier transform‐infrared spectroscopy analyses. The swelling and degradation of the matrix beads were found to be influenced by the pH of medium. Higher degrees of swelling were observed in intestinal pH than in stomach pH. Accordingly, the drug release study showed that the amount of SD released from the acacia gum–calcium alginate beads was higher in intestinal pH than in stomach pH. Therefore, the in vitro drug release from the SD‐loaded beads appears to follow the controlled‐release (Hixson‐Crowell) pattern involving a case‐2 transport mechanism operated by swelling and relaxation of the polymeric blend matrix.     

Drug release of pH/temperature-responsive calcium alginate/poly(N-isopropylacrylamide) semi-IPN beads

A series of semi-interpenetrating, polymer network (semi-IPN), hydrogel beads, composed of calcium alginate (Ca-alginate) and poly(N-isopropylacrylamide) (PNIPAAM), were prepared for a pH/temperature-sensitive drug delivery study. The equilibrium swelling showed the independent pH- and thermo- responsive nature of the developed materials. At pH=2.1, the release amount of indomethacin incorporated into these beads was about 10% within 400 min, while this value approached to 95% at pH=7.4. The release rate of the drug was higher at 37 degrees C than that at 25 degrees C and increased slightly with increasing PNIPAAM content. These results suggest that the Ca-alginate/PNIPAAM beads have the potential to be used as an effective pH/temperature sustainable delivery system of bioactive agents. [GRAPHS: SEE TEXT] A summary of the temperature- and pH-dependence on the release of the drug over a period of 450 min. The effect of the temperature on the swelling of the beads is shown in the inset.     

Biomineralized polysaccharide beads for dual-stimuli-responsive drug delivery

Biomineralized polysaccharide-coated alginate beads containing PNIPAAM were prepared. The resulting beads can be used as carriers for sustained pH/temperature-sensitive drug delivery. Characterizations using SEM, EDS, FTIR, and POM revealed that the beads were covered by the calcium-phosphate-mineralized alginate/chitosan membrane. The drug-release behavior was examined using indomethacin as a model drug, and the release profile of the developed materials was found to be responsive to pH and temperature. The release profile could be sustained under neutral conditions, indicating that the mineralized polysaccharide membrane could prevent the permeability of the encapsulated drug and reduce the drug release rate.     

Designing Swellable Beads of Alginate and Gelatin for Controlled Release of Pesticide (Cypermethrin)

In the present study biopolymeric beads of sodium alginate and gelatin were prepared by employing CaCl₂ as a crosslinking agent. A series of such microspheres of different compositions were prepared by varying the amounts of sodium alginate, gelatin and CaCl₂ in the feed mixture. The beads were loaded with an insecticide like cypermethrin. The prepared loaded and unloaded beads were characterized by FTIR spectral and Environmental scanning electron microscopy (ESEM) techniques, to gain insight into the molecular structure and morphology of beads, respectively. The swelling experiments were performed for different composition of beads and at varying pH and temperature of the swelling media. The swelling controlled release of insecticide was also investigated for 8 days in bi-distilled water as a release medium. The release experiments were performed under the static and varying experimental conditions and the data obtained were fitted to Fick's equation to evaluate diffusion coefficients of insecticide. The results were further analyzed by Fick's power law equation, and the possible mechanisms of the insecticide release were explored at different experimental conditions. Soil–pot experiments were also performed to demonstrate the applicability of the present controlled release technique to agricultural fields.     

Preparation and release profiles of pH/temperature-responsive carboxymethyl chitosan/P(2-(dimethylamino) ethyl methacrylate) semi-IPN amphoteric hydrogel

Thermo- and pH-responsive semi-IPN polyampholyte hydrogels were prepared by using carboxymethyl chitosan and P(2-(dimethylamino) ethyl methacrylate) with N N'-Methylenebisacrylamide (BIS) as crosslinking agent. It was found that the semi-IPN hydrogel shrunk most at the isoelectric point (IEP) and swelled when pH deviated from the IEP. Its swelling ratio dramatically decreased between 30 and 50 °C at pH 6.8 buffer solution. It also showed good reversibility. The UV results showed that when the pH values of drug release medium were 3.7, 6.8, and 9 at 25 °C, the cumulative release rates reached 83.1, 51.5, and 72.2%, respectively. The release rate of coenzyme A (CoA) was higher at 50 °C than 37 and 25 °C at pH 6.8 solution. The release rate decreased with increasing the content of carboxymethyl chitosan at 25 °C in pH 6.8 solution. The results showed that semi-IPN hydrogel seems to be of great promise in pH/temperature drug delivery systems.     

TEMPO-Oxidized Cellulose Beads as Potential pH-Responsive Carriers for Site-Specific Drug Delivery in the Gastrointestinal Tract

The development of controlled drug delivery systems based on bio-renewable materials is an emerging strategy. In this work, a controlled drug delivery system based on mesoporous oxidized cellulose beads (OCBs) was successfully developed by a facile and green method. The introduction of the carboxyl groups mediated by the TEMPO(2,2,6,6-tetramethylpiperidine-1-oxyradical)/NaClO/NaClO₂ system presents the pH-responsive ability to cellulose beads, which can retain the drug in beads at pH = 1.2 and release at pH = 7.0. The release rate can be controlled by simply adjusting the degree of oxidation to achieve drug release at different locations and periods. A higher degree of oxidation corresponds to a faster release rate, which is attributed to a higher degree of re-swelling and higher hydrophilicity of OCBs. The zero-order release kinetics of the model drugs from the OCBs suggested a constant drug release rate, which is conducive to maintaining blood drug concentration, reducing side effects and administration frequency. At the same time, the effects of different model drugs and different drug-loading solvents on the release behavior and the physical state of the drugs loaded in the beads were studied. In summary, the pH-responsive oxidized cellulose beads with good biocompatibility, low cost, and adjustable release rate have shown great potential in the field of controlled drug release.     

Study of Protein Adsorption/Adhesion Behaviors on Solid Beads Surface with Different Surface Properties

Three kinds of chitosan (CS) derivatives have been prepared via polyethyleneimine (PEI) or polyethylene glycol (PEG) together with PEI modified chitosan. FTIR, x-ray photoelectron spectroscopy (XPS), and thermal gravimetric analysis (TGA)/differential thermal analysis (DTA) proved the successful linkage, and XPS and zeta potential analysis show that these derivatives beads possess different surface nature. The PEI modified chitosan derivative is made in acid solution (A-PEI-CS) and the one added with additional PEG (PEG–CS-PEI) has showed higher swelling degree than their counterpart derivative prepared at basic condition (B-PEI-CS). Although the nitrogen content of A-PEI-CS is higher than that of B-PEI-CS, due to the better surface hydrophilicity, the B-PEI-CS beads are more capable of adsorbing bovine serum albumin (BSA) protein. Electrostatic attraction facilitates protein adsorption in a narrow acidic pH range while hydrophilicity hinders protein adhering to the beads’ surface at any pH.     

壳聚糖-g-聚甲基丙烯酸凝胶粒的制备及其药物释放行为

以壳聚糖和甲基丙烯酸为原料,硝酸铈铵为引发剂,合成了不同接枝率的壳聚糖-g-聚甲基丙烯酸(CS-g-PMAA),用FTIR、1H NMR和元素分析表征了产物的结构,以柠檬酸三钠和戊二醛为交联剂制备了具有核壳结构的CS-g-PMAA载药体系。 用UV/Vis检测了CS-g-PMAA粒子对模型药物的释放行为。 结果表明,CS-g-PMAA接枝率为12.21%时药物释放速率最慢,其在pH=1.8介质中药物累积释放量(11 h)为44.18%,而壳聚糖粒子的累积释放量高达65.24%,即接枝改性壳聚糖粒子对药物的缓慢控制释放性能较好; CS-g-PMAA粒子的释药行为还依赖于介质的pH值和盐浓度,在低pH值和低盐浓度下,药物释放速率较快;酶环境下由于载体材料的降解使药物释放速率加快。 分析了不同条件下CS-g-PMAA载药粒子中药物的释放机理。     

Carboxymethyl chitosan‐montmorillonite nanoparticles for controlled delivery of isoniazid: evaluation of the effect of the glutaraldehyde and montmorillonite

Chitosan, a natural biopolymer, is used for drug delivery application. But its potential application is limited by its low solubility in aqueous media. The present study was designed to prepare carboxymethyl chitosan (CMC), a water soluble derivative of chitosan, and evaluate the prospective of crosslinked CMC‐Montmorillonite (MMT) nanoparticles for controlled delivery of isoniazid. The nanoparticles were characterized by Fourier Transmission Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and Transmission emission microscopy (TEM). The effects of MMT and glutaraldehyde on nanoparticles were assessed with regard to encapsulation efficiency, percentage swelling degree, and cumulative release. Percentage swelling degree and cumulative release were studied in pH medium 1.2 and 7.4 for 6 h. The cumulative release was studied by UV‐visible spectrophotometer. Cell viability study was performed by MTT assay analysis. FTIR and NMR study indicated the successful preparation of CMC. FTIR study confirmed the interaction of MMT with CMC. The exfoliation of MMT layers and molecular level dispersion of isoniazid in CMC was examined by XRD and TEM. SEM study showed that the surface of the CMC‐MMT nanoparticles was smooth compared with those of CMC nanoparticles. Swelling and release of isoniazid from the nanoparticles increased with the decrease in the MMT and glutaraldehyde content. The percentage swelling degree and cumulative release was more in pH 1.2. Cell viability study revealed that CMC was not cytotoxic, and the nanoparticles containing MMT was less cytotoxic than those of MMT free nanoparticles. CMC‐MMT nanoparticles can be exploited as potential drug carrier for controlled release applications. Copyright © 2014 John Wiley & Sons, Ltd.     

Dynamic Release of Propranolol HCl from Cationic Ion–Exchanger–Loaded Calcium Alginate Beads

The dynamic release of drug propranolol HCl from the propranolol HCl–resin complex (PRC) loaded calcium alginate beads has been studied in the buffer media of pH 1.2 at the physiological temperature 37°C. The PRC encapsulated beads demonstrated nearly 58.04% release while naked PRC particles released 98.00% drug in 24 h in the gastric fluid. The amount of drug released was found to increase with and decrease in the amount of sodium alginate in the beads. Similarly, with the increase in the amount of entrapped PRC particles within the beads, the quantity of drug released was also observed to increase. The degree of crosslinking of beads also affected the release kinetics. Interestingly, the release from naked PRC particles followed ‘first‐order’ kinetics while PRC particles, entrapped in calcium–alginate beads, exhibited ‘diffusion controlled’ release behavior as indicated by liner nature of fractional release vs. √t plot.     

Properties of calcium-induced gel beads prepared with alginate and hydrolysates

Calcium-induced alginate gel beads (Alg-Ca) containing alginate hydrolysate, such as the guluronic acid block (GB), was prepared and the drug release profiles were investigated under simulated gastrointestinal conditions. The addition of GB to Alg-Ca altered its rheological properties. A model drug (hydrocortisone) was incorporated at 78% of its theoretical yield within the dried Alg-Ca containing 5% GB and it was gradually released from the beads in JP XIV 1st medium for disintegration test (pH 1.2), while it was rapidly released with disintegration of the gel matrix in JP XIV 2nd medium (pH 6.8). In contrast, for Alg-Ca containing GB and chitosan, disintegration was not observed in these media and the drug release rate was markedly different. These results demonstrate that the release profiles of drugs incorporated into Alg-Ca can be controlled by adding these polysaccharides.