Cell Biological and Biophysical Aspects of Lipid-mediated Gene Delivery

Cationic lipids are conceptually and methodologically simple tools to deliver nucleic acids into the cells. Strategies based on cationic lipids are viable alternatives to viral vectors and are becoming increasingly popular owing to their minimal toxicity. The first-generation cationic lipids were built around the quaternary nitrogen primarily for binding and condensing DNA. A large number of lipids with variations in the hydrophobic and hydrophilic region were generated with excellent transfection efficiencies in vitro. These cationic lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in the last decade delineated the cell biological basis of the cationic lipid gene delivery to a significant detail. The application of techniques such as small angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking the physical properties of lipid:DNA complex (lipoplex) with its intracellular fate. This biological knowledge has been incorporated in the design of the second-generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective strategies to overcome the various cellular barriers along with the lipoplex formulations methodologies. In this context, cationic lipid-mediated gene delivery is considerably benefited by the methodologies of liposome-mediated drug delivery. Lipid mediated gene delivery has an intrinsic advantage of being a biomimetic platform on which considerable variations could be built to develop efficient in vivo gene delivery protocols.     

Controlled Topical Delivery of Cyclosporin-a from Nonionic Liposomal Formulations: Mechanistic Aspects

Abstract

In a previous report (1), we showed that the rate and extent of uptake of cyclosporin-A (CsA) following topical application of nonionic liposomal formulations composed of glyceryl dilaurate (GDL), cholesterol (CH), and polyoxyethylene-10-stearyl ether (POE-10) into and through hairless mouse skin mounted on Franz diffusion cells could be controlled by varying the ratios of GDL to POE-10 (CH being held constant at 15 wt%). However, the pathways of transport as well as the dominant factors that control drug delivery from these formulations are not well understood. In this report, we describe results from studies similar in design to that reported earlier but using the melted form of the lipid components as a vehicle for transport of CsA into and through hairless mouse skin. The results suggest that the transport of CsA from liposomal formulations into and through the skin occurs as a result of dehydration of the liposomes followed by melting of the lipid components on the skin. Microautoradiographic studies suggest that CsA is predominantly transported via the pilosebaceous pathway.