Preparation and Evaluation of Photocrosslinkable Chitosan as a Drug Delivery Matrix S.R. Jameela, S. Lakshmi, Nirmala R. James, A. Jayakrishnan Polymer Chemistry Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Satelmond Palace Campus, Trivandrum 695 012, India Received 15 December 2001; accepted 24 January 2002 Published online 00 Month 2002 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/app.111122 ABSTRACT: Epichlorohydrin (1-chloro-2,3-epoxypropane) was reacted with sodium azide in the presence of a phase transfer catalyst to obtain 1-chloro-2-hydroxy-3-azidopropane, which was further coupled onto chitosan to prepare a pho- tocrosslinkable derivative of the biopolymer. Elemental analy- sis and infrared (IR) spectroscopy confirmed the incorporation of azide groups onto chitosan. Films were cast from an aque- ous acetic acid solution of azidated chitosan containing a model drug, such as theophylline. Irradiation of the film with ultraviolet (UV) light led to crosslinking of the drug incorpo- rated film. IR spectra indicated complete surface crosslinking within 2 h of irradiation. Release of theophylline from un- crosslinked and crosslinked films was examined in simulated gastric and intestinal fluids without enzymes at 37 °C. The release of the drug from the crosslinked films was slower than the release from uncrosslinked films. Although the system is far from being optimized to obtain sustained release of a phar- macologically active agent for long periods, the data obtained indicate the possibility of developing photocrosslinkable ma- trices of biopolymers, such as chitosan, for sustained drug delivery with many advantages over chemical crosslinking. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 00: 000-000, 2002 Key words: INTRODUCTION Chemical crosslinking is an important method to con- trol drug release from diffusion-controlled polymeric drug delivery matrices. Thus, hydrogels, proteins, and polysaccharides have been crosslinked using a num- ber of crosslinking agents to manipulate the diffusion of an entrapped pharmacologically active agent from such polymeric matrices. 1–4 Although bifunctional vi- nyl monomers, such as ethyleneglycol dimethacrylate and N,N’-methylene bisacrylamide, have been used as crosslinking agents for the preparation of synthetic hydrogels from polyacrylamide and poly(2-hydroxy- ethyl methacrylate), etc., crosslinking agents, such as glutaraldehyde, formaldehyde, terephthaloyl chlo- ride, 2,3-butanedione, epichlorohydrin, dicyclohexyl carbodiimide, etc., have been used for crosslinking drug delivery matrices derived from proteins and polysaccharides. Chitosan is a deacetylated derivative of chitin, a biopolymer second in abundance to cellulose. Many biomedical applications of chitosan have been envis- aged in the literature. 5,6 Among them is the possibility of using this polysaccharide as a matrix for sustained drug delivery. In a series of papers from this labora- tory, it was demonstrated that glutaraldehyde crosslinking of chitosan reduces the lysozyme suscep- tibility of chitosan to biodegradation and therefore could be used as a vehicle for prolonged delivery of drugs spanning weeks or months. 7–11 Chemical modification of chitosan have been exten- sively carried out because of the presence of active amino and hydroxyl groups in this biopolymer. There are, however, only very few references in the literature on the preparation of a photocrosslinkable chitosan derivative. Thus, a photoactive chitosan derivative has been synthesized using 4-azido pyridine derivatives for protein immobilization. 12 Covalent immobilization of chitosan onto polymeric film surfaces was carried out by attaching a photosensitive reagent 4-azidoben- soimidate by Aiba et al. 13 Recently, Ono et al. 14 re- ported the preparation of a photocrosslinkable chi- tosan for wound dressing application by incorporat- ing aromatic azides onto the polymer. Although photocrosslinking is a technique widely used in the coating industry, 15 there is very little in- formation in the published literature on the use of this technique for controlled drug delivery. Anderson et al. 16 used photosensitive ammonium dichromate to crosslink poly(2-hydroxyethyl methacrylate) films containing hydrocortisone succinate by UV radiation. If the drug carrier polymer itself contained photolabile functions, it may offer many advantages over chemi- cal crosslinking or crosslinking induced by photosen- sitizers. For example, activities of drugs such as sal- butamol, epinephrine, etc., are affected by aldehyde crosslinking of protein matrices such as albumin. 17 Correspondence to: A. Jayakrishnan (dr_jayakrishnan@ yahoo.co.in) Journal of Applied Polymer Science, Vol. 00, 000-000 (2002) © 2002 Wiley Periodicals, Inc. AQ: 1 AQ: 2 tapraid5/8e-polyapp/8e-polyapp/8e-orig/8e7542d02a sweigarm S=7 6/19/02 13:03 Art: 10756