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 μm 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.