title: Chitosan-aprotinin coated liposomes for oral peptide delivery: Development, characterisation and in vivo evaluation.
abstract: 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 4.5microm and the initially negative zeta potential (ca. -90mV) of the core liposomes switched to a positive value after polymer coating (ca. +40mV). 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.
authors.affiliation: Gifu Pharmaceutical University, Laboratory of Pharmaceutical Engineering, 5-6-1 Mitahora Higashi, 502-8585 Gifu, Japan.
authors.forename: Martin
authors.initials: M
authors.lastname: Werle
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000269:Adhesives / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D002116:Calcitonin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D008081:Liposomes; D008297:Male; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000269:Adhesives; D008081:Liposomes; D011108:Polymers; D011480:Protease Inhibitors; D002116:Calcitonin; D048271:Chitosan; D007611:Aprotinin; D002118:Calcium