In vitro and in vivo studies of controlled release of novel peptide from in situ polymer precipitation delivery system

Abstract

The in situ polymer precipitation delivery system has generated much interest over the last two decades. The ease of manufacturing and administering the delivery system are key advantages that have contributed to its increasing preference as a mode of drug delivery. Although much research has been performed on this system, the number of studies that have translated into animal models and subsequently into clinical trials is much lower than desired. This study aimed to investigate and understand the release mechanism and kinetics involved in peptide release from an in situ polymer precipitation system. Moreover, this study aimed to establish a correlation between the in vitroand in vivo-derived data. The ultimate aim was to identify a delivery system that can be used to deliver a novel therapeutic peptide, CD-NP, for the treatment of heart failure conditions. This study can be divided into 3 broad categories. First, in vitro studies were performed to characterise systemically the delivery system and its efficacy at achieving the prolonged release of the drug Cenderitide. Various gel formulation parameters were tested, i.e., the effect of polymer concentration, co-solvent, drug-loading and injected volume. The co-solvent system using the gel formulation 40% PLGA / 40% NMP / 20% triacetin was the most suitable for achieving the desired linear peptide release profile. Investigation of the solvent efflux and its influence on the drug release profile and shell structure formation morphology were also investigated. The Abstract x | P a g e solvent efflux and shell structure formation were found to be interdependent and affected the drug release profile. Second, feasibility studies were performed on both healthy and diseased Wistar rats. As