291789 Transdermal Administration of Therapuetics Using pH Sensitive Liposomes

Monday, October 29, 2012
Hall B (Convention Center )
Shiv Shah, Rutgers University, Piscataway, NJ

The stratum corneum (the outermost layer of the epidermis of the skin) is the main barrier to the successful transdermal delivery of drugs because the continuous layers of free lipids in its brick and mortar type structure prevent chemicals from passively entering the body through the skin.  Liposomes have been reported to be good candidates for the transdermal delivery of drugs because they penetrate the stratum corneum.

Our study evaluates the retention of pH sensitive liposomes under acidic conditions and the release of contents and pH sensitivity under pH neutral conditions of different compositions of liposomes.  Our liposomes are composed of lipids containing a cationic headgroup (trimethylammonium-propane-TAP), a neutral headgroup (Phosphytidyl choline- PC), a pH titratable headgroup (Phosphatidic Acid- PA) and nonmatching alkyl tail lengths.  The titratable headgroup is neutral under acidic conditions and as conditions turn more neutral, it starts becoming anionic.  The TAP and the now anionic PA are attracted each other by ionic charge interactions and this forms heterogeneous domains that have leaky interfaces along the nonmatching tail lengths.  The pH sensitivity is dependent on the amount of heterogeneous domains in the liposome which is dependent on how protonated the PA headgroup is (since the PA is more protonated under acidic conditions, less heterogeneous domains are formed since more PA is neutrally charged and the liposome retains its contents under acidic conditions).  These liposomes have the potential to be excellent drug carriers for transdermal delivery.


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