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Article # : SC12

Sema Çalış, Ph.D.

Professor

Biodegradable microspheres as depot system for parenteral delivery of peptide drugs

Rahul C. Mehta, Ramasubbu Jeyanthi, Sema Çalış**, B.C. Thanoo, Kevin W. Burton, Patrick P. DeLuca*

University of Kentucky College of Pharmacy, Rose Street #33 3, Lexington, KY 40536. USA

Summary

Synthetic biodegradable polymers of lactic and glycolic acid have been extensively investigated for sustained drug delivery. Drug release from lactide/glycolide polymers can be either diffusion controlled or matrix erosion controlled. Polymer degradation was dependent on the molecular weight of the polymer and matrix structure of the delivery system. High surface area, lower particle size and lower bulk density increased the rate of degradation. Gamma irradiation of the delivery system also increased the rate of matrix erosion by reduction of molecular weight. Microspheres containing peptide, salmon calcitonin (sCT), were prepared by solvent extraction techniques using temperature or dilution. sCT was also incorporated into pre-formed microspheres by adsorption. sCT has a strong hydrophobic region and hence can bind to the polymer by a combination of hydrophobic and ionic forces, resulting in high incorporation from an aqueous medium. Adsorption appeared to result in multiple layers of adsorbed peptide on the polymer surface. The microspheres with entrapped sCT exhibited in vivo release of sCT between days 5 and 9, whereas microspheres with adsorbed sCT showed low but detectable in vivo release for 3-4 days. Combination of microspheres with different release properties can be used to achieve various in vivo serum profiles.

Key words

Biodegradable microsphere; Peptide; Lactide/glycolide polymer; Salmom calcitonin; Drug delivery