Insertion of poly(ethylene glycol) derivatized phospholipid into pre‐formed liposomes results in prolonged in vivo circulation time

FEBS Letters

Zhu, George Z.²  Daniel, Barbra E.²  Allen, Theresa M.¹  Newman, Mary S.²  Mendez, Cecilia J.²  Uster, Paul S.² 

[1] Department of Pharmacology, 9–31 Medical Sciences Building, University of Alberta, Edmonton T6G 2H7, Canada;SEQUUS Pharmaceuticals, Inc., 960 Hamilton Court, Menlo Park, CA 94025, USA

关键词: Liposome;    Poly(ethylene glycol);    Insertion;    Critical micellar concentration;    Pharmacokinetics;    AUC;    area under the concentration-time curve;    5;    6-CF;    5;    6-carboxyfluorescein;    CH;    cholesterol;    CMC;    critical micellar concentration;    DPPG;    1;    2-dipalmitoyl-sn-glycero-3-phosphoglycerol;    sodium salt;    DTPA-DSPE;    N-diethylenetriaminepentaacetic acid-1;    2-distearoyl-sn-glycero-3-phosphoethanolamine;    sodium salt;    HSPC;    hydrogenated soy 1;    2-diacyl-sn-glycero-3-phosphocholine;    MPEG1900-DSPE;    N-carbamyl-methoxypoly(ethylene glycol)-1;    2-distearoyl-sn-glycero-3-phosphoethanolamine;    sodium salt;    1900 Da methoxy poly(ethylene glycol) fraction;   

DOI  :  10.1016/0014-5793(96)00452-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Transfer of MPEG₁₉₀₀-DSPE from micellar phase to pre-formed liposomes imparts long in vivo circulation half-life to an otherwise rapidly cleared lipid composition. MPEG₁₉₀₀-DSPE transfers efficiently and quickly in a time and temperature dependent manner. There is negligible content leakage and a strong correlation between assayed mol% MPEG₁₉₀₀-DSPE, liposome diameter increase, and pharmacokinetic parameters such as distribution phase half-life. Since a biological attribute (liposome clearance rate) can be modified by the insertion process, it suggests a simple and economical way to impart site-specific targeting to a variety of liposome delivery systems. This method is also a convenient way to measure the ‘brush’ thickness of such conjugates directly.

【 授权许可】

Unknown