PLGA-PEG-PLGA Tri-Block Copolymers as In Situ Gel-Forming Peptide Delivery System: Effect of Formulation Properties on Peptide Release

Various controlled peptide and protein delivery systems have been investigated for their potential for treatment of chronic diseases. In situ gelling systems are very attractive due to their biocompatibility, biodegradability, and simple manufacturing processes. The objective of this work was to investigate the effect of different excipients on release profile of calcitonin as a model protein from PLGA-PEG-PLGA thermally reversible gels. PLGA-PEG-PLGA with the ratio of PLGA to PEG equal to 2.5 was synthesized and characterized by ¹H NMR and gel permeation chromatography (GPC). The PLGA-PEG-PLGA polymeric solutions (25% w/w) containing calcitonin (0.05% w/w) and other excipients in various concentrations were prepared, and drug release from the thermally reversible gels was evaluated. It was shown that drug release from the systems was dramatically reduced when PEG 200 or PEG 1000 was added to the systems. This may be due to the effect of PEG as an internal cross-linking agent or the formation of PEG complexes that decrease the rate of drug release. Sodium laurel sulfate (SLS) was also shown to reduce the rate of drug release from the systems. This may be due to the large ionic heads of SLS that attract counterions of calcitonin. It can be concluded that the drug release rate from the systems can be controlled by using different excipients.