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AAPS PharmSciTech

, 20:307 | Cite as

Whole-Eye Perfusion Model for Screening of the Ocular Formulations via Confocal Laser Scanning Microscopy

  • Shallu Kutlehria
  • Arvind Bagde
  • Nilkumar Patel
  • Mandip SinghEmail author
Rapid Communication

Abstract

Various physiological, anatomical barriers make ocular drug delivery very challenging. Hence, better in vitro screening models are needed for rapid screening of the formulations. In this study, a simple whole-eye perfusion model was designed and its application was explored for screening targeted formulation across the full-thickness cornea using confocal laser scanning microscopy. PEG-cholecalciferol-based integrin targeted coumarin-6 micelles (TC6M) and non-targeted coumarin-6 micelles (NTC6M) were developed by solvent diffusion evaporation technique. The formulations NTC6M and TC6M had particles size 23.5 ± 5 nm and 28.5 ± 6 nm respectively and osmolality of 294–300 mOsml/Kg. The whole-eye perfusion model was developed using porcine eye. TC6M and NTC6M were instilled on the excised porcine eyes as well as in the eyes of NZW rabbits. Corneas were excised from the experimental eyes; coumarin-6 penetration across the corneas was analyzed using confocal microscope. Coumarin-6-loaded micelles had particle size below 50 nm. NTC6M formulations showed penetration to the deeper layers up to 500 μm porcine eyes and up to 50 μm in rabbit corneas. However, TC6M formulations exhibited superior retention, as higher fluorescent intensities were observed in upper layers up to 50 μm depth in the porcine eye and 20 μm depth in rabbit eye. Hence, applicability of whole-eye perfusion model in preliminary screening of the formulations was successfully demonstrated. Whole-eye perfusion model when combined with confocal microscopy has potential to be used as an efficient tool for rapid screening and optimization of various ophthalmic formulations.

KEY WORDS

perfusion model micelles confocal ocular coumarin-6 

Notes

Acknowledgments

We thank Dr. Imran Vohra for his technical guidance. We are also thankful to Dr. Dmitry for providing access to the Confocal Laser Scanning Microscope in Maglab (FSU) and Mr. Howell (owner of Jhonston’s meat market Monticello, Fl) for providing porcine eyes.

Funding Information

This project is supported by NSF-CREST Center for Complex Materials Design for Multidimensional Additive Processing (CoManD) award # 1735968 and Research Center in Minority Institute (RCMI) U54, 2454MD007582-34A1 grant

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Shallu Kutlehria
    • 1
  • Arvind Bagde
    • 1
  • Nilkumar Patel
    • 1
  • Mandip Singh
    • 1
    Email author
  1. 1.College of Pharmacy and Pharmaceutical SciencesFlorida A&M UniversityTallahasseeUSA

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