ELSEVIER zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Biomateriols zyxwvutsrqponmlkji 17 (1996) 61-66 0 1995 zyxwvutsrqponmlkjihgfedcbaZ Elsevier Science Limited Printed in Great Britain. All rights reserved 0142.9612/96/$15.00 Effect of liposome-albumin coatings on ferric ion retention and release from chitosan beads zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC Thomas Chandy” and Chandra P. Sharma Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal institute for Medical Sciences and Technology, Poojappura, Trivandrum - 695012, lndia Ferric chloride was embedded in a chitosan matrix to develop a prolonged-release form. The in vitro release profiles of ferric ions from chitosan beads were monitored in 0.1 M Tris-HCI buffer, pH 7.4, using a UV spectrophotometer. The amount of drug release was much higher initially, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with liposome and albumin coatings. From scanning electron microscope studies, it appears that the ferric ions diffuse out slowly to the dissolution medium through the micropores of the chitosan matrix. Further, the liposome forms a phospholipid membrane layer in the pores of chitosan beads and encapsulates the ferric ions within their vesicles and controls the release profile. The chitosan beads loaded with ferric ions substantially inhibited the polyurethane-associated calcification, in an in vitro model system. The released ferric ions, appeared to alter the protein-surface binding and improved the biocompatibility of the matrix. The results propose the possibility of modifying the polymer matrix to obtain a desired controlled release of the drug for a prolonged period. Keywords: Chitosan beads, ferric chloride, drug delivery, liposome modification, polyacrylamide gel electrophoresis Received 14 November 1994; accepted 20 March 1995 The development of improved methods of drug delivery has received a lot of attention in the last two decades. In many cases a constant effective non-toxic level of the drug at a particular body location is needed. Hydrogels based on polypeptides and polysac- charides have been widely investigated for therapeutic drug targetinglm3. Chitosan, a natural polysaccharide prepared from the chitin of crabs and lobsters, is biodegradable and biocompatible435, and has been used in several sustained-release preparations6-8. Ferric ions are one of the most prominent trivalent metal ions, tried extensively to inhibit tissue-associated calcificationgZ lo. Previous work demonstrated that pretreatment of tissue with FeCl, had effectively inhibited the calcification profile, possibly via blocking the calcium phosphate crystallization” . The regional controlled release of Fe3+ or A13+ from the polyurethane matrix” , has also demonstrated a reduction in calcium deposition to implants. Recently, Golomb et ~1.~ have proposed the formulation and the in vivo efficacy of prolonged controlled-release chitosan matrices contain- ing an anticalcification agent. Previous research indicates that the molecular event initiating the interaction between flowing blood and a non-biological surface is the spontaneous adsorption of Correspondence to Dr T. Chandy. a thin film of proteins and subsequent attachment of platelets and thrombus formation’2.13. Various matrices loaded with drugs have been commonly investigated at blood-tissue interfaces to study their drug delivery profiles. However, the effects of these loaded drugs on the matrix and on modulating the protein-surface binding have not been elucidated. In the present study, FeCl,-loaded microbeads were prepared by employing chitosan as the carrier, and the surfaces were modified with lyposomes and albumin. The versatility of sustained delivery devices using this polymer is suggested from studies of the matrix structure and the in vitro release profile. Further, it appears that the Fe3+-loaded chitosan matrix can modulate the surface-protein binding, which has been extended in the initial observations presented here. zyxwvutsrqpon MATERIALS AND METHODS M aterials Chitosan (a(1+4)2-amino-Z-deoxy-P-D-glucan), which is one of the abundantly available polysaccharides in nature, was obtained as a gift from the Central Institute of Fisheries Technology (Cochin, India). Chitosan, 61 Biomaterials 1996, Vol. 17 No. 1