Tacrolimus is an emerging candidate for the treatment of immune-mediated inflammatory ocular disorders (IIODs) however its ocular delivery remained a challenge due to its hydrophobic nature, high molecular weight and physiological and anatomical constraints of the eye. The present work describes vesicles composed of propylene glycol, phospholipid and water, proglycosomes (PNVs), as novel carriers for ocular delivery of tacrolimus. Addition of propylene glycol decreases vesicle aggregation, increases encapsulation of tacrolimus and prevented drug leakage. Developed PNVs were of nanosize (111.5±3.2nm) and 5-fold more elastic than conventional liposomes. PNVs showed prolonged drug release over period of 12h and higher corneal permeation, 5-fold and 13-fold, compared to conventional liposomes and tacrolimus solution, respectively. Studies in rabbits demonstrated prolonged precorneal retention (upto 8h) and manifestly improved intraocular drug levels, well above therapeutic levels, at all tested time-points following topical application of PNV formulation compared to drug solution. Further, PNVs were found to be safe for ocular use. In conclusion, the developed PNVs are prospective carriers for enhanced ocular delivery of tacrolimus.
Keywords: Liposomes; Ocular biodistribution; Proglycosomes; Propylene glycol; Schirmer strip; Tacrolimus.
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