Combination Nanotherapeutics for Dry Eye Disease Treatment in a Rabbit Model.

Abstract

PURPOSE:

Anti-inflammation is essential for dry eye disease. Traditional anti-inflammation agent corticosteroids applied in dry eye disease (DED) treatment could result in high intraocular pressure, especially in long-term treatment. Thus, we have prepared a liposome loading 1-bromoheptadecafluorooctane and tetrandrine (PFOB@LIP-Tet) to treat DED via anti-inflammation that hardly affects intraocular pressure in this study, which provided another therapy strategy for dry eye disease.

METHODS:

We firstly detected the physicochemical properties of PFOB@LIP-Tet. Next, we tested the biosafety of synthesized liposomes for corneal epithelium. Then, we explored the accumulations and distribution of PFOB@LIP-Tet both in cellular and animal models. And then, we assessed the therapeutic effects of PFOB@LIP-Tet formulations by laboratory and clinical examinations. Last, we examined the changes in eye pressure before and after treatment.

RESULTS:

PFOB@LIP-Tet and Tet showed a characteristic absorption peak at 282 nm while PFOB@LIP did not. Large amounts of PFOB@LIP-Tet remained on the ocular surface and accumulated in the corneal epithelial cells in DED rabbits. Corneal staining scores of DED rabbits respectively treated by ATS, PFOB@LIP-ATS, Tet-ATS and PFOB@LIP-Tet-ATS for seven days were 3.7±0.5, 3.2±0.4, 1.5±0.5 and 0.5±0.5. The expressions of related cytokines were correspondingly downregulated significantly, indicating that the inflammation of DED was successfully suppressed. The intraocular pressure changes of DED rabbits before and after treatment by PFOB@LIP-Tet showed no statistical significance.

CONCLUSION:

We successfully synthesized PFOB@LIP-Tet, and it could effectively treat dry eye disease via anti-inflammation but hardly affected the intraocular pressure.

• Authors: Liandi Huang, Huanhuan Gao, Zhigang Wang, Yixin Zhong, Lan Hao, Zhiyu Du
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 16 Pg. 3613-3631 ( 2021) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 34079253 (Publication Type: Journal Article)
• Copyright: © 2021 Huang et al.

Chemical References

• Benzylisoquinolines
• Cytokines
• Liposomes
• tetrandrine

Topics

• Animals
• Benzylisoquinolines (administration & dosage, adverse effects, therapeutic use)
• Cytokines (metabolism)
• Disease Models, Animal
• Drug Interactions
• Dry Eye Syndromes (drug therapy, metabolism, pathology)
• Epithelium, Corneal (drug effects, pathology)
• Intraocular Pressure (drug effects)
• Liposomes
• Nanomedicine
• Rabbits