Physical-Chemistry Characteristics and Biodistribution of Poly(ethylene glycol)-Coated Liposomes Using Poly(oxyethylene) Cholesteryl Ether

Abstract

Poly(ethylene glycol)-coated liposomes were prepared with poly(oxyethylene) cholesteryl ethers (mPEG-Chol). PEG unit numbers tested were 50, 100 and 200, of which the average molecular weights (m) of PEG were 2200, 4400 and 8800, respectively. Properties of both PEG-coated liposomes and PEG-Chol molecules were investigated. These liposomes exhibited a long circulation time in the blood after i.v. injection in rats, estimated by both the lipid membrane marker, L-α-dipalmitoylphosphatidylcholine [2-palmitoyl-9,10-3H] (3H-DPPC), and an internal aqueous marker, 3H-inulin. Accumulation in the liver and spleen at 8 h-post-injection was significantly reduced compared with conventional liposomes. The percentage of PEG-Chol incorporation in liposomal membranes was also investigated. Liposomes composed of egg yolk phosphatidylcholine (EPC)/PEG-Chol at various molar ratios were separated from free PEG-Chol molecules, which are not incorporated in liposomal membranes by chromatography over Sepharose CL-4B columns. PEG-Chol incorporation reached approx. 14 and 18 mol% of the total lipids with 25% PEG-Chol unit numbers of 200 and 50, respectively. The occupied area per molecule of PEG-Chol was larger than that of Choi, and the fluorescence anisotropy (r) of the initial 25mol% 8800PEG-Chol liposomes was smaller than that observed for 12.5 mol% Choi liposomes. PEG-coated liposomes containing calcein were incubated at 37 °C in heat-inactivated fetal bovine serum (FBS). In the presence of FBS, calcein leakage was increased with PEG-Chol percentage incorporation and an increase in FBS concentration. The amount released from PEG-coated liposomes represented 60% at maximum and was larger than that of the control liposomes. PEG-Chol molecules are interesting compounds since they can be easily synthesized in a large amount on an industrial scale. The basic physical-chemistry characteristics investigated in this article are critical to assess the pharmacological application of PEG-Chol liposomes as drug delivery systems. © 1995, The Pharmaceutical Society of Japan. All rights reserved.