Do interactions with phospholipids contribute to the prolonged retention of polypeptides within the lung?

McAllister, S.M., Alpar, H.O., Teitelbaum, Z. and Bennett, D.B. (1996) Do interactions with phospholipids contribute to the prolonged retention of polypeptides within the lung? Advanced Drug Delivery Reviews, 19 (1). pp. 89-110. 10.1016/0169-409X(95)00101-C.

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DOI: 10.1016/0169-409X(95)00101-C


Several amphipathic or Hydrophobic polypeptides exhibited prolonged retention in the lung following pulmonary administrations. The physicochemical basis for prolonged retention remains uncertain but may be related to hydrophobic and electrostatic interactions between the polypeptides and the phospholipids of lung tissues. The pulmonary absorption characteristics of detirelix, polymyxin B, and cyclosporin A were reviewed in relation to their interactions with phospholipids. Phospholipid interactions were evaluated qualitatively by comparison of the efficiencies of polypeptides' incorporation into liposomes, and by a quantitative comparison of the polypeptide affinities for immobilized artificial membranes (IAM). Detirelix and cyclosporin A exhibited prolonged pulmonary retention compared with polymyxin B. Those observations correlated with the polypeptides' liposomal incorporation efficiencies and IAM affinities. The duration of absorption of all three polypeptides was further extended following pulmonary administration of their liposomal formulations. A fourth polypeptide, lipopeptide L-693,989, was identified as possessing the structural hydrophobicity sufficient to interact strongly with phospholipid bilayers: a possible explanation for its prolonged pulmonary retention.

Item Type:Article
Uncontrolled Keywords:Author Keywords: Polypeptide delivery; Lung; Detirelix; Polymyxin B; Cyclosporin A; Lipopeptide; Phospholipid; Liposome; Immobilized artificial membrane chromatography
Departments, units and centres:Department of Pharmaceutics > Department of Pharmaceutics
ID Code:2110
Journal or Publication Title:Advanced Drug Delivery Reviews
Deposited By:Library Staff
Deposited On:20 May 2011 14:11
Last Modified:20 May 2011 14:11

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