ABSTRACT
OBJECTIVE: To develop a bioadhesive nanostructured lipid carrier (P407-NLC) for ocular delivery of cyclosporine A and investigate its ocular distribution in rabbits. METHODS: Melt-emulsification method was chosen to prepare CsA-NLC. Poloxamer 407 (P407) was dissolved in borate buffer solution (pH 8.0), then added into CsA-NLC to prepare P407-NLC. The morphology of P407-NLC was observed by transmission electron microscopy (TEM). The mean particle size and Zeta potential were measured by laser particle size analyzer. The viscosity was measured by rheometer. Dialysis method was employed to investigate the in vitro release of CsA from P407-NLC at 34°C. The concentrations of CsA in ocular tissues were studied by RP-HPLC, and the pharmacokinetic parameters were calculated by linear trapezoidal method. The topical ocular irritation study of P407-NLC was carried out in rabbits. RESULTS: The obtained P407-NLC was approximately spherical in shape with average particle size of (41.2 ± 0.2) nm and Zeta potential of (-15.2 ± 0.21) mV, and P407 was coated on the appearance of NLC. P407-NLC was non-newtonian fluids. The in vitro release of CsA from P407-NLC was slowed down and fitted well with single exponential distribution model. AUC0-24h of CsA in cornea, aqueous humor and iris after ocular administration of P407-NLC containing 6.0% P407 were 10.75, 4.45 and 4.62 times higher than that of CsA oil solution, and 2.77, 1.22 and 1.54 times higher than that of CsA-NLC, respectively. MRTs in aqueous humor, cornea and iris were 3.28, 2.26 and 3.46 times higher, respectively, than that of CsA oil solution, and 1.69, 1.50 and 1.62 times higher than CsA-NLC, respectively. There was no irritation for P407-NLC to rabbit eyes. CONCLUSION: P407-NLC can be used to increase the level of CsA in ocular tissues and would be a promising nanocarrier for ocular drug delivery. Copyright 2012 by the Chinese Pharmaceutical Association.