439i Elastic Moduli of Unilamellar Ether-Lipid Vesicles Estimated Using Multi Angle Laser Light Scattering

James R. Springstead and Harold G. Monbouquette. Chemical & Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA 90095

Lipid vesicles (liposomes) are emerging as one of the leading drug delivery systems in recent times due to the potential ability to control spatial and temporal distribution of the released drug. However, vesicles of the commonly used diester lipid type exhibit high leakage rates and low stabilities. Better liposome characterization methods and compositions are needed if liposomes are to be implemented clinically as drug delivery vehicles.

Archaeoglobus fulgidus, a thermophilic archaeon with previously uncharacterized core lipids, has membranes composed of diether and tetraether lipids that are more stable at higher temperatures than the standard diester lipids of non-thermophilic organisms. After finding methods to consistently isolate, purify, and hydrolyze the lipids of this organism, the core lipid composition has been characterized over a range of growth temperatures using LC-MS. Preliminary data suggests that the ratio of tetraether to diether lipid in A. fulgidus increases with growth temperature. The ether lipids give rise to vesicles that are more stable at higher temperatures than those of the standard diester lipids. The osmotic swelling of liposomes has previously been measured to estimate their elastic moduli using several techniques including micropipette aspiration and dynamic light scattering. Multi angle laser light scattering (MALLS), coupled with Rayleigh-Gans-Debye theory, has been shown to accurately estimate the geometric radii of standard diester lipid vesicles. Liposomes of ester and ether lipid are made via detergent dialysis and characterized by MALLS. The osmotic swelling is monitored to estimate the elastic moduli of the respective vesicle types. These techniques are used to compare the elasticity of ester and ether lipid vesicles, as well as vesicles formed from lipid extracts of A. fulgidus grown at different temperatures.

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