Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis

Abstract

Iontophoresis is a promising technique for enhancing transdermal administration of charged drugs. However, conventional iontophoresis is not sufficient for effective delivery of large, hydrophilic, or electrically neutral molecules. In this study, we utilized charged liposomes as carriers, focused on a transfollicular route for delivery of the liposomes, and optimized iontophoretic conditions and lipid composition for this method in both in vitro and in vivo conditions.As a result, we identified the optimum condition (lipid composition:DOTAP/EPC/Chol=2:2:1, current supply: 0.45 mA/cm 2 , duration: 1 hr) for effective iontophoretic delivery of aqueous solution, which can not be transferred into the skin without charged liposomes. We also examined the pharmacological effects of iontophoresis of liposomes encapsulating insulin (INS-lipo) using a rat model of type I diabetes. Interestingly, iontophoresis of INS-lipo onto a diabetes rat skin resulted in a gradual decrease in blood glucose levels, with levels reaching 20% of initial values at 18 hr after administration. These lower blood glucose levels were maintained for up to 24 hr. Significant amount of insulin were also detected in plasma 18 hr after iontophoresis of INS-lipo. We succeeded in developing a non-invasive and persistent transfollicular drug delivery system that used a combination of liposomes and iontophoresis.

Superoxide Dismutase-Loaded Solid Lipid Nanoparticles Prepared by Cold Homogenization Method: Characterization and Permeation Study Through Burned Rat Skin

“…They believed that penetration of liposomes with a diameter greater than 100 nm through the stratum corneum is difficult due to the narrow intracellular space. The same results were reported about insulinencapsulated liposomes (24). Also Lasch et al (25) indicated fluorescent-labeled lipid of liposomes applied over the stratum corneum and didn't penetrate in the skin after 24 hours.…”

Effects of liposomes with polyisoprenoids, potential drug carriers, on the cardiovascular and excretory system in rats

“…Over the past decade, liposomal drug delivery systems were used by many researchers and various applications were reported, such as targeted gene therapy [11,25], transfollicular [15] or ophthalmic [20] drug delivery. In many cases DOPE (dioleoyl phosphatidylethanolamine), an analogue of the native PE with a defined fatty acid composition, was used in liposomal formulations.…”

Promotion of the transdermal delivery of protein drugs by <em>N</em>-trimethyl chitosan nanoparticles combined with polypropylene electret

“…The supernatant containing BSA or SOD was determined by reversed-phase high-performance liquid chromatography (HPLC) or micro BCA Kit (Pierce). 37 The EE was calculated using the following equation 2:…”