Chitosan Nanoparticles for the Linear Release of Model Cationic Peptide

The present study is focused on the development of a model drug delivery system (DDS) based on Chitosan (CS) nanoparticles using Renin substrate I (RSI) as model agent. RSI shares the main chemical-physical features of several biologically active antimicrobial peptides (AMPs). AMPs have a great therapeutic potential that is hampered by their lability in the biological fluids and as such they are perfect candidates for DDS. The development studies of quality DDS loaded with AMPs would require highly sensitive and specific quantification assays. The use of RSI allowed for the fine-tuning and optimization of the formulation parameters to promote the hydrophobic interactions between CS and the cationic peptide, favour the loading of the active ingredient and enhance the release properties of the carrier. RSI was encapsulated in chitosan NPs by mean of ionic gelation and a chromogenic enzymatic essay was carried out for the release kinetics evaluation. The developed formulations displayed almost 100% of encapsulation efficacy, low burst percentages, and a linear release of the model peptide. A release model was created showing a direct dependence on both the amount of RSI and NPs radius. Although CS has always been formulated with negatively charged active agents (e.g. oligonucleotides or anionic proteins), the use of ionotropic gelation in presence of a small cationic active agent promoted the formation of core-shell NPs. The described model, with tuneable linear release rates, appears eligible for further exploitation such as the loading of therapeutically active AMPs.