Positively charged polymeric nanoparticles improve ocular penetration of tacrolimus after topical administration

Tacrolimus (TAC) is an immunosuppressant with potential use in ophthalmology, especially as a steroid sparing agent. The efficacy of TAC has been investigated in the treatment of different anterior segment inflammatory disorders. However, its use is limited by its poor corneal penetration, which has led to the development of different nanocarriers. In order to overcome this limitation, we prepared positively charged polymeric nanoparticles loaded with tacrolimus (TAC-NPs) for topical ocular application. TAC-NPs were prepared by interfacial polymer deposition following solvent displacement method, using Eudragit (R) RL100, a cationic polymer. The formulation was characterized and the ocular safety was assessed in vivo by Draize eye test and histopathological analysis. TAC was quantified in aqueous humor to determine the in vivo release of the nanoparticles. TAC-NPs presented suitable physical-chemical characteristics for ocular application, including monomodal size distribution with a mean diameter of 104 +/- 1 nm, positive zeta potential and mucoadhesive properties. The monitoring of the physical-chemical characteristics and the multiple light scattering analysis of TAC-NPs suggested their long-term stability. The in vivo safety investigation of TAC-NPs and blank-NPs showed no signs of ocular irritation on the ophthalmological examination and histopathological study, indicating the biocompatibility of this carrier. The nanoparticles were able to deliver TAC for over 36 h with a better performance than the drug suspension. The in vivo release profile of TAC-NPs indicated slower elimination with 1.7-fold higher maximum concentration of TAC and 5.3-fold higher AUC, suggesting increased ocular penetration and bioavailability in addition to extended delivery. TAC-NPs improved the ocular delivery of tacrolimus after topical administration, without causing any ocular irritation. It shows the potential of this carrier as an alternative for ocular delivery of tacrolimus in the treatment of anterior segment inflammatory conditions.