Chandra P. Sharma

Chitosan-as a Biomaterial

Chitosan [a (1----4) 2-amino-2-deoxy-beta-D-Glucan] is a unique polysaccharide derived from chitin. Several attempts have been made to use this biopolymer in biomedical field. The use of this material in the development of hemodialysis membranes, artificial skin, drug targetting and other applications are discussed. It appears, this novel biomolecule, biodegradable, and biocompatible, find applications in substituting or regenerating the blood/tissue interfaces. This polysaccharide having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour.

Use of chitosan as a biomaterial: Studies on its safety and hemostatic potential

Chitosan, a mucopolysaccharide of marine origin, was studied for its safety and hemostatic potential. Its surface was treated with glutaraldehyde, carbodiimide, and plasma glow discharge to elicit effects of enzyme degradation. Of the seven enzymes used, leucine amino peptidase caused maximum degradation. Autoclaving appeared to be an ideal sterilizing method as it caused least decrease in tensile strength and effected a negligible rate of hemolysis. Sterilizing with glutaraldehyde with a physiologic pH retained the maximum tensile strength of chitosan. In vivo toxicity tests indicated that it is nontoxic, and the sterilized films were free of pyrogen. Coagulation and hemagglutination tests showed that the hemostatic mechanism of chitosan seems to be independent of the classical coagulation cascade and appears to be an interaction between the cell membrane of erythrocytes and chitosan.

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.

Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption

In this work a novel chitosan derivative, lauryl succinyl chitosan (LSC) was developed for the purpose of evaluating its applications towards oral peptide delivery system. Nano/microparticles were developed from this derivative by sodium tripolyphosphate (TPP) cross linking. Human insulin was used as the model protein drug and the release kinetics was studied at gastrointestinal pH. The presence of succinyl carboxyl groups had inhibitory effect on the release kinetics of insulin at pH 1.2 minimizing up to about 8.5+/-0.45% in two hours. Results showed that the presence of hydrophobic moieties controlled the release of the loaded insulin from the particles at intestinal pH. The particles were negatively charged with size ranging from 315 nm to 1.090 microm. The mucoadhesive capacity was established ex vivo using the jejunum of rat intestine. Confocal microscopy studies proved the tight junction permeability in Caco 2 cells and in vivo uptake of the FITC-insulin from loaded nanoparticles by the rat intestinal epithelium. The results demonstrated that the modified chitosan with both hydrophilic (succinyl) and hydrophobic (lauryl) moieties had improved the release characteristics, mucoadhesivity as well as the permeability of the insulin compared to the native chitosan particles. The LSC2 particles were capable of reducing blood glucose levels in diabetic rats for the duration of about 6 h. This indicated that this novel derivative could be a promising candidate for oral peptide delivery.

Chitosan matrix for oral sustained delivery of ampicillin

Ampicillin was embedded in a chitosan matrix to develop an oral release dosage form. The in vitro release profile of ampicillin from chitosan beads and microgranules of chitosan was monitored, as a function of time, using a UV Spectrophotometer. The releasing studies were performed in a rotating shaker at 100 r.p.m., containing 0.1 M HCI buffer, pH 2.0, or 0.1 M phosphate buffer, pH 7.4, solutions, and a comparison was made between the drug loaded microbeads and microgranules. It seems that the amount and percentage of drug release was much higher in HCI solution compared with the phosphate solution, probably due to the gelation properties of the matrix at acid pH. The release rate of ampicillin from the chitosan matrix was slower for the beads as compared with the granules. From scanning electron microscopic studies, it appears that the drug forms a crystal structure within the chitosan beads, which dissolves out slowly to the dissolution medium through the micropores of the chitosan matrix. The results propose the possibility of modifying the formulation in order to obtain the desired controlled release of the drug for a convenient oral sustained delivery system.

Review Paper: Absorbable Polymeric Surgical Sutures: Chemistry, Production, Properties, Biodegradability, and Performance:

Among biomaterials used as implants in human body, sutures constitute the largest groups of materials having a huge market exceeding

Chitosan beads and granules for oral sustained delivery of nifedipine: in vitro studies

1.3 billion annually. Sutures are the most widely used materials in wound closure and have been in use for many centuries. With the development of the synthetic absorbable polymer, poly(glycolic acid) (PGA) in the early 1970s, a new chapter has opened on absorbable polymeric sutures that got unprecedented commercial successes. Although several comparative evaluations of suture materials have been published, there were no serious attempts of late on a comprehensive review of production, properties, biodegradability, and performance of suture materials. This review proposes to bring to focus scattered data on chemistry, properties, biodegradability, and performance of absorbable polymeric sutures.

Ceramic drug delivery: a perspective.

Nifedipine was embedded in a chitosan matrix to develop a prolonged-release form. The in vitro release profiles of nifedipine from chitosan beads and microgranules were monitored by UV spectrophotometer. The studies were performed in a rotating shaker (100 rev min-1) in 0.1 M HCl buffer (pH 2.0) or 0.1 M phosphate buffer (pH 7.4). Comparison was made between drug-loaded microbeads and microgranules. The amount and percentage of drug release were much higher in HCl than in phosphate buffer, probably due to the salt formation of the matrix (chitosan hydrochloride) at acid pH. The release rate of nifedipine from chitosan matrix was slower for beads than granules. These findings suggest the possibility of modifying the formulations to obtain the desired controlled release of the drug in an oral sustained-delivery system.

Cyclodextrin complexed insulin encapsulated hydrogel microparticles: An oral delivery system for insulin

Different ceramic substances are offered in the market as bone substitute materials. These include monophasic calcium phosphate ceramics of tricalciumphosphate (TCP) or hydroxyapatite (HA), biphasic calcium phosphate ceramics and multiphasic bio-glasses synthetic calcium phosphate cements. Ceramics with appropriate three-dimensional geometry are able to bind and concentrate bone morphogenetic proteins in circulation and may become osteoinductive (capable of osteogenesis) and can be effective carriers of bioactive peptide or bone cell seeds and are therefore potentially useful in tissue engineering and drug delivery. An attempt has been made to review various drug delivery applications of ceramics.

Oral delivery of therapeutic protein/peptide for diabetes – Future perspectives

An oral insulin delivery system based on methyl-β-cyclodextrin (MCD) complexed insulin encapsulated polymethacrylic acid (PMAA) hydrogel microparticles was evaluated in this investigation. Poly(methacrylic acid)-chitosan-polyethylene glycol (PCP) microparticles were prepared by ionic gelation method. The insulin-MCD (IC) complex prepared was characterized by fluorescence spectroscopic and isothermal titration micro-calorimeteric (ITC) methods. MCD complexed insulin was encapsulated onto PCP microparticles by diffusion filling method. Loading and release properties of the complexed insulin from microparticles were evaluated under in vitro conditions. The effect of MCD complexation on the permeability of insulin was studied using Caco 2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. In vivo experiments were carried on streptozotocin induced diabetic rats to evaluate the efficacy of MCD complexed insulin encapsulated PCP microparticles to deliver insulin by the oral route. IC complex formation was established by fluorescence and ITC investigations. Insulin loading and release properties from the hydrogel matrix was rather unaffected by the MCD complexation. However MCD complexation was effective in enhancing insulin transport across Caco 2 cell monolayers, when applied in combination with the PMAA hydrogel system. Both insulin and MCD complexed insulin encapsulated PCP microparticles were effective in reducing blood glucose level in diabetic animal models. Cyclodextrin complexed insulin encapsulated hydrogel microparticles appear to be an interesting candidate for oral delivery of insulin.