Abstract
A dialysis method for the preparation of large volumes of stable and homogeneous bilayer liposomes under sterile conditions was developed. The equipment consists of a disposable hemodialysis capillary dialyzer connected to two reservoirs through which the micelle/liposome solution is pumped in a closed circuit. The detergent is removed by a countercurrent flow of the dialysis buffer. Homogeneous, detergent fjree liposome preparations totaling 100 ml with lipid concentrations ranging from 5 to 25 mg/ml can be prepared within 2-4 hours. Greater lipid concentrations or larger batch volumes can be obtained with dialyzing cartridges allowing for higher detergent clearing performances.
The incorporation of lipophilic derivatives of the cytostatic drugs 1β-D-arabinofuranosyl cytosine (ara-C) and 5′-fluoro-2′-deoxy uridine (FUdR) is nearly quantitative, and stable, homogeneous bilayer liposomes of about 100 nanometers in diameter are obtained. Liposomes with prodrug concentrations of 2 to 10 mg per milliliter can be prepared depending upon the lipid amounts used. Free ara-C or generally small and water soluble molecules however, cannot be encapsulated within the liposomes due to quantitative loss during dialysis.
Get full access to this article
View all access options for this article.