Formulation of Nano and Micro PLGA Particles of the Model Peptide Insulin: Preparation, Characterization, Stability and Deposition in Human Skin

The primary objective of this study was to develop a particulate formulation for peptide delivery that would provide enhanced peptide stability, controlled release and the potential for targeting to specific tissues. Biodegradable hydrophobic particles were prepared from poly (D,L-lactide-co-glycolide) (PLGA) by both solvent evaporation and solvent diffusion methods. Bovine insulin was chosen as a model peptide for formulation development and evaluation. By forming a complex between insulin and protamine, 50% incorporation of the model peptide in PLGA particles was achieved and a sustained release of insulin was observed over one week with improved stability of insulin in the PLGA matrix. The formation of an insulin-protamine complex and the method of manufacture are important determinants of the physicochemical characteristics of the particles formed. Preliminary evaluation of the deposition of the particles within skin was determined by fluorescent images following topical application to excised human skin. Microparticles with size above 7 μm remained on the surface of the skin. Nanoparticles (<1 μm) showed permeation into the viable epidermis and dermis with deposition concentrated around the hair follicles and sebaceous glands.