Enhancement of the Ocular Therapeutic Effect of Prednisolone Acetate by Liposomal Entrapment

Eye drops account for 90% of ophthalmic formulations despite of the rapid precorneal drug loss. Our aim is to test the effect of positive charge induction and the subsequent size reduction on the efficiency of liposomes as ocular drug delivery system for the lipophilic drug prednisolone acetate (PSA). Different formulations of PSA-loaded liposomes, positive multilamellar liposomes (pMLV), positive small (nano-sized) unilamellar liposomes (pSUV) and neutral multilamellar liposomes (nMLV), were prepared. These formulations were characterized by measuring surface charge, size distribution, entrapment efficiency, release rate, and ability to deliver PSA across the cornea. In vitro studies showed that positive charge induction reduces the transcorneal flux (about 1.9-fold lower than nMLV), while the subsequent size reduction results in higher flux (about 1.2-fold higher than nMLV). But in vivo results revealed that pSUV produced more concentrations of PSA in aqueous humor than nMLV (P < 0.05) suggesting greater chance for drug penetration, pSUV were more effective than nMLV in this regard (P < 0.05). As revealed by in vivo studies and ophthalmic examinations, positive charge induction and the subsequent size reduction increased the efficiency of liposomes as ocular drug delivery system for PSA.