Sintese de fosfatidilcolinas diacetilenicas, preparação e caracterização de lipossomas polimerizados para aplicações na liberação controlada de medicamentos




Development of liposome applications has been limited by lipid bilayer instability, mainly for in vivo applications. Polymerizable lipids leads to more stable liposomes afier polymerization process, which represents a promising altemative for drug delivery by the oral administration route specially. In this work, diacetylenic polymerizable phoshpolipids analogous to phosphatidylcholine were synthesized, purified and caracterized. Diacetylenic groups were located at different positions in acyl chains with the same lenght (23 carbon atoms), or located at the same position in acyl chains with different lenght, generating the following phospholipids: 1,2-bis(heptadeca-l O, 12-diynoyl)-sn-glycero-3 phosphatidylcholine (DCS,3PC, Ia), 1,2-bis(tricosa-4,6-diynoyl)-sn-glycero-3­phosphatidylcholine (DC2,ISPC, Ic), and 1,2-bis(tricosa-lO,12-diynoyl)-sn-glycero­3-phosphatidylcholine (DCS,9PC, Ib). Small unilamellar vesicles (SUV) were prepared ITom pure diacetylenes and polymerized by ultra-violet (UV) radiation. Liposomes were characterized by their lipid contents, hydrodynamic radius, polymerization kinetics and stability in the presence of surfactants. Synthesis of DCS,9PC, the only commercially available and the most used polymerizable diacetylenic phospholipid, was reached, as well as the synthesis of two new molecules, DCs,JPC and DC2,lsPC. Innovation introduced in the synthesis process has lead to its improvemment by using environrnenta11ess aggressive reagents and obtention of more stable intermediate compounds. Changes on diacetilenic group positioning and acyl chain length generated lipid bilayers with different physical­chemical properties. Polymerized liposomes were more stable than the corresponding monomeric liposomes. Insaturations of the polymeric conjugated chain could be reduced by reaction with diimide molecules. The trapping ability of hydrophilic drugs in the lipid aggregates was evaluated for the tubercu1ostatic isoniazid


acetileno polimeros lipossomos fosfatideos

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