Technological Development of Lipid-Based Microcylinders: Biocompatibility and Controlled Release

Abstract

We have developed a lipid-based microcylinder for the controlled release of biological response modifiers. Lipid microcylinders are composed of 1,2-ditricosa-10,12-diynoyl-snglycerol-3-phosphocholine which form hollow cylinders 50–250 μm in length with a diameter approximately 0.5–1.0 μm. Amphiphilic molecules such as ganglioside (5–6 mol%) can be incorporated into the bilayers of the microcylinder, modulating surface characteristics of the structure.

In this study, we have examined the biocompatibility of lipid microcylinders and lipid microcylinders containing 6 mol% ganglioside. The interaction of microcylinders with peripheral blood monocytes and three cell lines: U937, a histocytic monocyte; K562, an erythroblast, and; a Jurkat derivative, a lymphoblast was assessed. Toxicity, as measured by proliferative status of the cell lines, was not evident at lipid concentrations up to 100 μg/ml lipid. Peripheral blood monocytes were observed to closely associate, but not engulf lipid microcylinders. However, when ganglioside was present in the lipid microcylinders this interaction was markedly decreased.

We have begun to measure the release rates of growth factors such as transforming growth factor-beta (TGF-ß) from lipid microcylinders. Release of TGF-ß from the microcylinders follows first-order kinetics. The rate of release can be modulated by increasing the temperature which results in a thermotrophic phase transition of the lipid at 43°C.