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

[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.

[学科分类] 生物化学/生物物理

[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