In vitro and in vivo evaluation of an in situ gel forming system for the delivery of PEGylated octreotide

The objective of this study was to develop a controlled delivery system for PEGylated octreotide using a Poloxamer based in situ gel forming polymer. PEGylated octreotide kept its full biological activity and higher serum half-life compared to the original octreotide. The designed drug delivery system contained low concentration of Poloxamer 407 (P407) (<0.16%) with polyvinyl alcohol (PVA) as a polymeric additive. Rheological measurements of gel vehicle formulations indicated that the in situ gel forming system with optimum sol-gel transition temperature of 28.7 degrees C could be formed using a combination of P407 and PVA at ratio of 15-10% (w/v). The effect of formulation additives such as buffering agents on rheological behavior demonstrated that sodium bicarbonate and lactic acid have opposite effect on sol-gel transition temperature of the system. Using buffering agents, it was possible to shift the sol-gel transition to lower or higher temperatures. The in vitro release profiles of octreotide and PEGylated octreotide from the selected P407/PVA formulations were measured using a membrane-less device. PEGylated octreotide showed slower release rate from the gel system with different release kinetic compared to octreotide. In animal studies, a sustained release rate was achieved with both PEGylated and non-PEGylated octreotide, but longer delivery was observed for PEGylated octreotide. Tissue histopathological studies confirmed the biocompatibility of the delivery system for PEGylated octreotide, supporting the suitability of P407/PVA mixture as an injectable drug delivery system. The total effects of increasing PEGylated peptide half-life and prolonged release from thermoresponsive gel system offer the potential for sustained delivery of PEGylated octreotide. (C) 2012 Elsevier B.V. All rights reserved.