Tacrolimus (TAC)-loaded Ploy-lactide-co-glycolide nanoparticles (PLGA-NPs) was developed by emulsification-diffusion method for topical ocular delivery in certain ocular conditions where therapeutic level of immunomodulator into eyes is required for sufficient duration. So, we optimized TAC-loaded PLGA-NPs with higher TAC payload. The mean particle-size and its distribution, polydispersity, zeta-potentials, morphology, drug encapsulation and loading capacity of NPs were analyzed. Transcorneal permeation through excised rabbit cornea revealed instant and controlled permeation of TAC from TAC-aqueous suspension (TAC-AqS) and from PLGA-NPs, respectively. Stability study results indicated that there were no significant changes in above characteristics for 1-month storage at 25°C. The safety of PLAG was established by modified Draize's test after its topical administration in rabbit eyes. The adopted liquid chromatography-electrospray ionization tandem mass spectrometry was successfully applied for TAC quantification in ocular tissues and aqueous-humor. PLGA-NPs improved corneal, conjunctival and aqueous humor bioavailability of TAC. A considerably higher TAC-concentration from F2 was found in ocular tissues even at 24h and in aqueous humor till 24h following its topical ocular administration as compared to TAC-AqS. The PLGA-NPs significantly enhanced ocular bioavailability of TAC than that of aqueous suspension.
Keywords: Nanoparticles; Ocular autoimmune diseases; Ocular biodistribution; Ocular irritation; Ploy-lactide-co-glycolide; Tacrolimus; Transcorneal permeation.
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