Chitosan-aprotinin coated liposomes for oral peptide delivery: Development, characterisation and in vivo evaluation

In order to improve the systemic uptake of therapeutic peptides/proteins after oral administration, the polymer-protease inhibitor conjugate chitosan-aprotinin was synthesised and polyelectrolyte complexes between negatively charged multilamellar vesicles (MLV)and positively charged chitosan-aprotinin conjugate were prepared. It could be demonstrated that chitosan-aprotinin was capable of significantly inhibiting Trypsin in vitro in concentrations of 0.05% and 0.1%, whereas no inhibition was observed in the presence of 0.1% chitosan. The size range of the prepared MLV was between 3 and 4.5 mu m and the initially negative zeta potential (ca. -90 mV) of the core liposomes switched to a positive value after polymer coating (ca. +40 mV). Confocal laser microscopy studies showed comparable mucoadhesive properties of chitosan-aprotinin coated MLV and chitosan coated MLV. In comparison to calcitonin in solution, the area above the blood calcium concentration-time curve (AAC) after oral administration of calcitonin loaded chitosan coated MLV to rats increased around 11-fold, and around 15-fold in the case of calcitonin loaded chitosan-aprotinin coated MLV. Data gained in the current study are believed to contribute to the development of novel polymer-protease inhibitor based delivery systems. (C) 2008 Elsevier B.V. All rights reserved.