Evaluation of pharmacological efficacy of 'insulin-surfoplex' encapsulated polymer vesicles

The present study has been designed to study whether formation of ion-pair complex or 'surfoplex' can enhance the pharmacological efficacy of protein-loaded PCL-PEG-based polymerosomes. Insulin was selected as the model protein and was complexed with sodium deoxycholate, a naturally occurring bile salt. The surfoplexes were characterized for extent and site of complexation, stability, mass and partition coefficient. The lipophilicity of insulin was enhanced 5-fold upon complexation resulting in an increase in entrapment efficiency by 10-50% for all formulations compared to free insulin. The release of insulin from the systems was also modulated with reduction in burst release by 30%. The surfoplex was found to be therapeutically active for 8h duration (C(max) serum insulin=64.15+/-13.28 mIU/mL) in diabetic rat model. However, pharmacological efficacy of the complex-loaded nanoparticles (Nps) did not show significant enhancement with respect to insulin-loaded systems. The study therefore suggests that while ion-pair complexes may improve the in vitro kinetics of protein-loaded carriers, their therapeutic potential is dependent on the intensity of interactions between the peptide chains and polymer matrix.