Enhanced bioavailability and retinal accumulation of lutein from self-emulsifying phospholipid suspension (SEPS).

摘要

Ability of any formulation to keep the drug in solubilized form in vivo is essential for bioavailability (BA) enhancement rather than the solubility of drug in the formulation vehicle/matrix itself. Besides, utilization of an excess amount of surfactants/co-surfactants to solubilize the drug in the lipid formulation poses potential pharmaceutical as well as health problems. To address this problem, self-emulsifying phospholipid suspension (SEPS) consisting of high amount of phospholipid (an endogenous lipid with efficient in vivo emulsification capability) and relatively low amount of surfactant/co-surfactant has been proposed to enhance the bioavailability (BA) of lutein. In this study, the ability of SEPS formulation to enhance the BA of lutein was assessed from three SEPS formulations with various amounts of phospholipid (SEPS-0, SEPS-I, and SEPS-II with 0mg, 250 mg, and 500 mg of Phosal 53 MCT, respectively) in beagle dogs following a single oral administration of lutein equivalent to 100mg, and were compared with commercial formulation (CF). In addition, the retinal accumulation of lutein in Sprague Dawley (SD) rats' eyes from SEPS-II formulation (lutein dose of 100mg/kg/day) was investigated following single daily oral administration for a period of 14 days. CF and placebo (vegetable oil without lutein) were also administered for the same period of time and were compared with the SEPS-II formulation. In the relative BA study in beagle dogs, no significant differences were observed between the pharmacokinetic (PK) parameters of formulation SEPS-O and CF. However, the C(max) in comparison to CF was 3.70 folds and 11.76 folds higher for SEPS-I and SEPS-II, respectively. Relative BA compared to CF was 178.88% and 473.13% for SEPS-I and SEPS-II, respectively. The retinal lutein accumulation was 0.91 +/- 0.31 ng/g, 3.45 +/- 1.63 ng/g, and 14.72 +/- 2.02 ng/g for placebo, CF, and SEPS-II, respectively. This enhancement was about 16.1 folds and 4.27 folds compared to placebo and CF, respectively. The relative BA study in dogs and retinal accumulation study in rats demonstrated the excellent ability of SEPS to enhance the BA of lutein. For this reason, SEPS containing lutein could be a promising lipid based delivery system for the prevention of ocular diseases.