302 Asparagine Derived Lipid Analogues Stabilizes Liposomes in Acidic Environment

Thursday, November 5, 2009: 2:40 PM
Ballroom C+D (Camino Real Hotel)
Adelphe M. Mfuh , Department of Chemistry, University of Texas at San Antonio, San Antonio, TX
Mathew P. D. Mahindaratne , Department of Chemistry, University of Texas at San Antonio, San Antonio, TX
George R. Negrete , Department of Chemistry, University of Texas at San Antonio, San Antonio, TX
Frederick J. Lakner , Chemical Diversity Inc, San Diego, CA
Liposomes are artificial nanocapsules that have an increasing importance as a new modality for drug delivery. Despite the numerous reports on this subject, there is no technology in use that addresses the oral administration of liposome-encapsulated therapeutic materials. This limitation is partly due to the degrading effect of lytic enzymes and also the acidity of the gastrointestinal tract. The design of liposomal formulations that can tolerate such environments will represent a breakthrough in the field of drug delivery and even beyond. We therefore report the synthesis, characterization, and self-assembly of seven members of a novel class of asparagine-derived lipid analogues (ALA) and their potentials in the stabilization of phospholipid nanocapsules under acidic conditions. In this work, we utilized high resolution optical microscopy (HROM), photon correlation spectrometry (PCS), turbidometry, attenuated total internal reflection Fourier transform infrared spectroscopy (ATR-FTIR), and scanning electron microscopy (SEM) to investigate the physical integrity of the nanocapsules formulated with different composition of disteroylphosphadityl choline (DSPC) and ALA at different pH media. Based on our results, DSPC liposomes were stabilized by these novel lipids in acidic environments at pH as low as 1.9.