Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera.
A challenge in ocular drug delivery is to maintain the therapeutic concentration of a drug at the site of action in the eye. The objective of the present study was to investigate the feasibility of micellar carrier systems for sustained drug delivery in transscleral iontophoresis in vitro. Simple and mixed micelles prepared using sodium taurocholate (TA) alone or with egg lecithin (LE) were the carrier systems studied. Dexamethasone (DEX), a poorly water soluble corticosteroid, was the model drug. The micellar carrier systems were first characterized for their solubilization and encapsulation of the drug. Passive and 2-mA iontophoretic (both cathodal and anodal) transport experiments were conducted using these micellar carrier systems in side-by-side diffusion cells with excised human sclera in vitro. Drug release studies were performed after the transport experiments. Saturated DEX solution without the micellar carriers was used as a control. It was found that the solubilization capacity of the micellar carrier systems increased as the total lipid concentration of the systems increased. Drug release from the sclera was significantly prolonged with the micellar carrier systems as compared to the control after passive and iontophoretic delivery. Less than ~20% of DEX was released from the sclera in approximately 2h after cathodal iontophoretic delivery of the micellar carrier systems, whereas more than ~50% of DEX was released from the control in the same time period under the same condition. Micellar carrier systems can be a suitable transscleral drug delivery system for poorly water soluble drugs by enhancing their aqueous solubilities and providing sustained drug delivery. These micellar carrier systems can be efficiently delivered into and across the sclera by iontophoresis for drug delivery.
Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA. choprap@mail.uc.edu
Poonam
P
Chopra
Jinsong
J
Hao
S Kevin
SK
Li
D002102:Cadaver; D002463:Cell Membrane Permeability; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005240:Feasibility Studies; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D008823:Micelles; D008954:Models, Biological; D010316:Particle Size; D012590:Sclera / Q000378:metabolism*; D012995:Solubility; D013499:Surface Properties
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005938:Glucocorticoids; D008823:Micelles; D003907:Dexamethasone