Pulmonary delivery of elcatonin using surface-modified liposomes to improve systemic absorption: polyvinyl alcohol with a hydrophobic anchor and chitosan oligosaccharide as effective surface modifiers.
The aim of this study was to investigate the feasibility of surface-modified liposomes for pulmonary delivery of a peptide. Chitosan oligosaccharide (oligoCS) and polyvinyl alcohol with a hydrophobic anchor (PVA-R) were used as surface modifiers. The effect of liposomal surface modification on the behavior of the liposomes on pulmonary administration and potential toxicity were evaluated in vitro and in vivo. In an association study with A549 cells, PVA-R modification reduced interaction with A549 cells, whereas oligoCS modification electrostatically enhanced cellular interaction. The therapeutic efficacy of elcatonin (eCT) after pulmonary administration to rats was significantly enhanced and prolonged for 48 h after separate administration with oligoCS- or PVA-R-modified liposomes. oligoCS-modified liposomes adhered to lung tissues and caused opening of tight junctions, which enhanced eCT absorption. On the other hand, PVA-R-modified liposomes induced long-term retention of eCT in the lung fluid, leading to sustained absorption. Consequently, surface modification of liposomes with oligoCS or PVA-R has potential for effective peptide drug delivery through pulmonary administration.
Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.
Mitsutaka
M
Murata
Koji
K
Nakano
Kohei
K
Tahara
Yuichi
Y
Tozuka
Hirofumi
H
Takeuchi
D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D006801:Humans; D008081:Liposomes; D008168:Lung / Q000378:metabolism; D008297:Male; D009844:Oligosaccharides / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution; D018675:Toxicity Tests
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D009844:Oligosaccharides; D011142:Polyvinyl Alcohol; D002116:Calcitonin; D048271:Chitosan; C012755:elcatonin