Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac

Abstract

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography–tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.

Summary points

• Ocular emulsion eyedrops containing bipartitioned oil droplets to entrap cyclosporin A (CsA) and etodolac (Edc) were prepared using castor, olive and silicon oils.

• The mean particle size, polydispersity index and zeta potential values observed for emulsions were 365.13 ± 7.21 nm, 0.282 ± 0.03 and 26.45 ± 2.09 mV, respectively.

• The drug-entrapment efficiency values of 77–82% were found for CsA and Edc in emulsions.

• A faster Edc release from emulsions was observed compared with CsA release in 7.4 pH simulated tear fluid.

• The combination index value of 0.806 computed from the in vitro protein denaturation assay indicates synergism in the anti-inflammatory activity of emulsions.

• The cell viability (%) values of 95.710 ± 2.78 to 99.263 ± 0.92% were noticed in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using human corneal epithelial cells.

• The ultraperformance liquid chromatography–tandem mass spectrometry bioanalytical method was utilized for the simultaneous estimation of CsA and Edc in ocular tissues of healthy rabbit eyes.

• The highest area under the curve from 0 to 90 min time period (AUC_0-90 min) values were obtained for CsA from emulsions in the cornea followed by conjunctiva, sclera, vitreous and aqueous humor.

• The highest AUC_0-90 min values were found for Edc from emulsion in the cornea, followed by the sclera, conjunctiva, aqueous humor and vitreous.

Keywords: :

• anti-inflammatory
• cyclosporin A
• dry eye disease
• etodolac
• nanosized emulsions

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The use of albino rabbits in the experimental procedure was permitted by the Institutional Animal Ethical Committee of National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India (NIPER/PE/19/23) on 11 September 2019. Moreover, the authors affirm that the rabbits used in the study were kept in accordance with the guidelines provided by the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research.