Prolongation of the Circulation Time of Doxorubicin Encapsulated in Liposomes Containing a Polyethylene Glycol-Derivatized Phospholipid: Pharmacokinetic Studies in Rodents and Dogs

Authors: Gabizon A.A.¹; Barenholz Y.²; Bialer M.³

Source: Pharmaceutical Research, Volume 10, Number 5, May 1993 , pp. 703-708(6)

Publisher: Springer

Abstract:

The pharmacokinetics of doxorubicin (DOX) encapsulated in liposomes containing polyethylene glycol-derivatized distearoylphosphatidylethanolamine (PEG/DSPE) were investigated in rodents and dogs. The plasma levels of DOX obtained with PEG/DSPE-containing liposomes were consistently higher than those without PEG/DSPE or when PEG/DSPE was replaced with hydrogenated phosphatidylinositol (HPI). Despite the inclusion of PEG/DSPE in liposomes, there was a significant drop in the plasma levels of DOX when the main phospholipid component, hydrogenated phosphatidylcholine, was replaced with lipids of lower phase transition temperature (dipalmitoylphosphatidylcholine, egg phosphatidylcholine), indicating that phase transition temperature affects the pharmacokinetics of liposome-encapsulated DOX. In beagle dogs, clearance was significantly slower for DOX encapsulated in PEG/ DSPE-containing liposomes than in HPI-containing liposomes, with distribution half-lives of 29 and 13 hr, respectively. In both instances, almost 100% of the drug measured in plasma was liposome-associated. The apparent volume of distribution was only slightly above the estimated plasma volume of the dogs, indicating that drug leakage from circulating liposomes is insignificant and that the distribution of liposomal drug is limited mostly to the intravascular compartment in healthy animals.

Keywords: liposome; doxorubicin; pharmacokinetics; polyethylene glycol

Language: English

Document Type: Regular paper

Affiliations: 1: Sharett Institute of Oncology, Hadassah University Hospital, P.O.B. 12000, Jerusalem 91120, Israel. To whom correspondence should be addressed. 2: Department of Membrane Biochemistry, Hebrew University–Hadassah School of Medicine, Jerusalem, Israel. 3: Department of Pharmacy, School of Pharmacy, The Hebrew University of Jerusalem, P.O.B. 12065, Jerusalem 91120, Israel.

Publication date: 1993-05-01

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• In this Subject: Pharmacology
• By this author: Gabizon A.A. ;  Barenholz Y. ;  Bialer M.

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