Novel Collagen Based Material for Local Drug Delivery Systems
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1008-T09-08
Novel Collagen Based Material for Local Drug Delivery Systems Luciano Castaneda, Suzanne Pluskat, Darline Ky, Earry Te, and Katarzyna Slowinska California State University, Long Beach, Long Beach, CA, 90840-3903
ABSTRACT In a search for new drug delivery matrix, the synthesis of a novel collagen material based on tiopronin (N-(2-Mercaptopropionyl)glycine) protected gold clusters (MPC) as a crosslinking agent is proposed. The structure of collagen matrix modified with MPC is studied using transmission electron microscope. The thermal properties are examined with differential scanning calorimetry. To assess the biocompatibility of the matrix, the cytotoxicity assays are conducted. INTRODUCTION Local drug delivery is the method of choice in treatment of tumors, bacterial infections, and bone regeneration.1 The advantages of local drug delivery are widely recognized.2 The collagen matrix is considered one of the most promising biomaterials for targeted drug delivery systems as well as for scaffolding and mechanical parts fabrication.3, 4 The collagen, fibrin and gelatin are naturally derived polymers utilized in the wound healing, bone regeneration and gene therapies. Biopolymers are often perceived as safer, readily available, capable of specific cell interactions and relatively inexpensive. The crosslinking of collagen improves its stability, prolongs its biodegradability time, and allows better control of the drug release profile.1,5 All currently used crosslinking procedures are based on formation of either zero-length linker or, on incorporation of the linear molecule into the matrix thus resulting in products that are structurally very similar to each other. On the other hand the formation of multiple-way linkers in the natural collagen (ìyoungî vs. ìagedî collagen) greatly influences the structure and performance of collagen in tissues.6 Recently the crosslinking of collagen with dendrimers (generations 0 through 3) was reported. The use of this 3-D crosslinker resulted in exceptional thermal stability of the matrix.7 Thus it is clear that further search for 3-D crosslinekers for collagen modification if of utmost importance. In a search for a new structural arrangement of the collagen matrix and to improve the mechanical properties of the matrix as well as to gain better control over the drug delivery rate (drug-matrix interactions) we used a new crosslinking agent based on a tiopronin protected (N(2-Mercaptopropionyl)glycine) gold nanocluster. In this approach we are able to express carboxyl groups of tiopronin on the surface of the 3-dimentional nanocluster. Tiopronin , a nonnatural amino acid renders the cluster water soluble, stable, and compatible with protein chemistry. Carboxylic groups of tiopronin react with the amino groups of the lysine residues of collagen (via (N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride) EDC coupling) resulting in multiple-way 3-D crosslinked material. The gold clusters serve as a good model of 3D linking center because of the ease of preparation and
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