Lipid-based microtubular drug delivery vehicles

Lipid microtubules that self-assemble from a diacetylenic lipid are suitabl e structures for the sustained release of bioactive agents. Microtubules we re loaded with agents under aqueous conditions and embedded in an agarose h ydrogel for localization at areas of interest. Protein release from our mic rotubule-hydrogel delivery system was characterized in vitro, and in vivo b iocompatibility was examined. The influences of protein molecular weight an d initial loading concentration on release profile were evaluated by releas ing test proteins myoglobin, albumin, and thyroglobulin. Protein molecular weight inversely affected the release rate, and loading with a higher prote in concentration increased the mass but not the percent of initially loaded protein released daily. Preservation of protein activity was demonstrated by the ability of a neurotrophic factor released from the delivery system t o induce neurite extension in PC12 cells. Bovine aortic smooth muscle cells co-cultured with the microtubule-hydrogel system showed no evidence of cyt otoxicity and proliferated in the presence of the microtubules. Subcutaneou s implantation of microtubules in rodents revealed no significant inflammat ory response after 10 days. Our microtubule-hydrogel system is useful for a pplications where sustained release without contact between agent and organ ic solvents is desired. (C) 2001 Elsevier Science B.V. All rights reserved.