In recent years, increasing attention has been given to the manner in which the drugs are delivered. Drugs are being incorporated into solid polymers in controlled and target release systems. In controlled release technology, biodegradable polymeric carriers offer potential advantages for prolonged release of macromolecular drugs. The drugs coming under this class include polypeptides, hormones, polysaccharides, antigens, antibodies and other biologically active agents. The polymer utilization is increasing day-by-day by the rapid growth of pharma manufacturers, growth in number of institutions and personal involved in teaching and research activities.
Basic characteristic of ideal polymer
The basic characteristic of an ideal polymer for healthcare includes inertness, compatibility with environment, non-toxicity, ease in administration, inexpensive to fabricate, and good mechanical strength. The selection criteria for polymer is based on properties such as solubility, synthesis ability, finite molecular weight, and narrow distribution. These properties provide compatibility and biodegradability to the drug attachment in drug polymer linkages.
The polymers can be classified based on its origin into natural polymer, synthetic polymer and further based on biodegradability into biodegradable and non-biodegradable polymers. The controlled release polymeric systems can be classified on the basis of the mechanism controlling the release of the incorporated drug into diffusion controlled systems, chemically controlled systems, and swelling controlled system. The increasing interest of novel materials in the medical and pharma fields, whether as prostheses or in medical devises designed for contact with the biological environment of the living body, has paved the way for exploring the potential of polymer applications. A number of biodegradable polymers as carriers have been investigated for the sustained release of macromolecular drugs. The polymers in this class include poly(lactic acid), poly(lactic acid-co-glycolic acid), poly(ortho-esters), poly(anhydrides), and poly(E-caprolactone). The natural polymers such as polysaccharides and proteins were extensively used for the delivery of low molecular weight drugs, but little attention was given to these polymers for macromolecular drugs. The reason may be due to the assumption that these polymers degrade in vivo rapidly limiting the delivery of these drugs for a short period of time.
Chitosan is a naturally occurring cationic biopolymer from the consequent commencing of the hydrolysis of chitin. It is a polysaccharide obtained from ecologically sound natural sources namely crab, outer skeleton of insects, lobsters, shrimp shell wastes and other invertebrates. The chitosan polymer is the second profuse polysaccharide subsequent to cellulose. The biocompatibility of chitosan polymer and the natural abundance of the material together make it useful in the pharmaceutical formulations.
The chitin is obtained by treating the shell with 2.5N NaOH at 75oC and with 1.7 N HCl at room temperature for 6 hours. The deacetylation of chitin can be done by alkaline treatment using NaOH at high temperature or by enzymatic reaction. The degree of deacetylation increases with increase in temperature and increase in concentration of NaOH. The polymer differ from chitin is that majority of the N-acetyl groups in chitosan are hydrolyzed. The degree of hydrolysis has a significant effect on the solubility and rheological properties of the polymer. The amino group on the polymer has a pKa value in range of 5.5 to 6.5 depending on source of the polymer. The chitosan is now available commercially in various molecular weights ranging from 50kDa-2000kDa with different degree of deacetylation (40-90%). The chitosan has received considerable attention as possible pharmaceutical excipient in both conventional and novel applications such as diluents in tablet, disintegrating agent, wet granulation, film coating, hydro gel, wetting agent, bio adhesive, sustain release of drugs, site specific drug delivery, vaccine delivery etc. The chitosan polymer is used in different field like agriculture as a natural seed treatment, plant growth enhancer and bio pesticide. The chitosan polymer can be used as haemostatic agent and in bandages. The chitosan polymer with polyurethane coating heals the scratches when exposed to sunlight offering promising result in scratch-free cars and other products. In healthcare, chitosan in tablet form is used as fat attractors or as dietary fibre.
Chitosan polymers were studied for colon-specific delivery to treat ulcerative colitis using 5-amino salicylic acid encapsulated in chitosan capsule. The colon specific oral delivery using chitosan succinate and chitosan phthalate were studied for improving the bioavailability of diclofenac sodium. The intestinal absorption of buserelin in vivo using a combination of chitosan hydrochloride and carbomer 934P can be a promising excipient for peroral delivery of peptide drugs. The chitosan as a polymeric vesicles drug carrier enhances the possibility of fabricating a drug delivery system for oral and intranasal administration of water soluble drug such as bleomycin. The study of ibuprofen by micellar system using N-palmitolyl chitosan(PLCS) have shown to be a good controlled delivery devise showing improved encapsulation efficiency. The anticancer drug, paclitaxel, to the tumour site using chitosan film has gained momentum in cancer therapy. The topical formulations containing 5-FU loaded liposome embedded into a structured vehicle of chitosan act as a reservoir for continuous delivery of the encapsulated drug. The chitosan based nanoparticle using hydroxylpropylcyclodextrins prepared by the ionic cross linking of chitosan with sodium tripolyphosphate in the presence of cyclodextrins offers a potential as a transmucosal delivery of hydrophobic compounds. The chitosan polymers attached with enzyme inhibitor give a promising system for delivery of sensitive peptide drugs like calcitonin. The nasal administration of drugs with chitosan and randomly methylated b-cyclodetrin showed enhanced absorption and elevate the bioavailability of estradiol. Chitosan offers a potential carrier for DNA complexation and used in non-viral vectors for gene therapy application, since chitosan protects against DNA degradation and leads to its condensation. The chitosan nanoparticles with the ability to entrap drugs or condensed plasmid DNA and has demonstrated efficacy in enhancing drug uptake and promoting gene expression. The use of chitosan/ tripolyphosphate nanoparticle as a sustained drug delivery system has showed good peptide absorption across mucosal surface and improves the protein loading.
The positive charged polysaccharide chitosan is able to increase the precorneal residence time of ophthalmic preparation when compared with simple aqueous solutions. The sustained delivery of interleukin-2(rlL-2) using chitosan microspheres, and showed system is suitable for delivery of (rlL-2). The study based on effect of chitosan oligomers on pulmonary absorption of interferon-alpha (IFN) by in vivo pulmonary absorption and showed a significant increase in IFN concentration in serum after intratracheal administration of (IFN) with these oligomers. The chitosan polymer is an excellent polymer for buccal delivery due to its muco/bioadhesive property and can increase the absorption of the chlorhexidine for enhancing its antibacterial activity. The periodontal delivery of drugs directly using chitosan has showed promising result and can be used for prolonged release of drugs into periodontal pocket. The floating systems having a density lower than the density of the gastric juice, prepared by chitosan granules with internal cavities prepared by deacidification and when added to acidic pH 1.2 provide immediate buoyant and control the release of prednisolone. These systems have long residence time and increase the bioavailability of drugs absorbed from upper part of GIT. The chitosan modified by thioglycolic acid to the primary amino group of the polymer are used for improving the residence time of clotrimazole in vaginal mucosa tissue for the treatment of mycotic infection.
The main objective of WHO’s vaccine initiative programme for children was to develop a safe single-dose vaccine. The synthetic biodegradable polymers were extensively investigated for the controlled delivery for vaccine and some of this category has regulatory approval for human use also. Only little attention was given for the development of vaccine using natural polymer, which are economical compared with synthetic polymer. The chitosan a natural polymer and susceptibility of chitosan to lysozyme makes it biodegradable in vivo. The cross-linked chitosan using a dialdehyde such as glutaraldehyde makes it less susceptible to degradation by lysozyme. The cross-linked chitosan microsphere may prove to be a good carrier for prolonged delivery of macromolecular drugs. The chitosan microspheres were prepared by emulsion cross-linking method and the vaccine antigen were incorporated by adsorption or by encapsulation procedure.
(Author is assistant professor, National College of Pharmacy, Manassery, Kozhikode 673 602, Kerala)