A Novel Eyes Topical Drug Delivery System: CsA-LNC for the Treatment of DED.

PURPOSE: The objective of the present work was to prepare safe and effective Ciclosporin A Lipid nanocapsule (CsA-LNC) eye-drops for the treatment of DED.

METHODS

The phase-inversion method was used to prepared different sizes CsA-LNC. CsA biodistribution in ocular after topical administration in rabbits was analyzed by a validated UPLC-MS/MS method. The efficacy of CsA-LNCs (25 nm, 50 nm, 85 nm) was evaluated using the tear breakup time, fluorescein staining, tear production, inflammatory cytokines and histopathology tests. The safety of CsA-LNCs was study by the score of ocular irritation and histological examination study.

RESULTS

CsA-LNCs(20-100 nm) were successfully prepared, An in vivo PK study showed significant improvement of the bioavailability (4.20-fold (25 nm), 2.15-fold (50 nm) and 2.33-fold (85 nm)) in bulbar conjunctiva, and great permeability was observed in the cornea for CsA-LNCs compared with CsA emulsion. An in vivo PD study showed that CsA-LNCs have great efficacy for DED, and the effect was improved over CsA emulsion. CsA-LNCs were safe and not cause significant irritation to the eyes surface of rabbits.

CONCLUSION

This work has demonstrated CsA-LNCs, in particular small sizes CsA-LNC, are safe and effective with promising potential to treat DED. Grapical abstract.