In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses

Ditixa T Desai; Furqan A Maulvi; Ankita R Desai; Manish R Shukla; Bhargavi V Desai; Avinash D Khadela; Kiran H Shetty; Dinesh O Shah; Mark D P Willcox

doi:10.1016/j.ijpharm.2021.121414

In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses

Int J Pharm. 2022 Feb 5:613:121414. doi: 10.1016/j.ijpharm.2021.121414. Epub 2021 Dec 22.

Authors

Ditixa T Desai¹, Furqan A Maulvi², Ankita R Desai², Manish R Shukla³, Bhargavi V Desai², Avinash D Khadela⁴, Kiran H Shetty², Dinesh O Shah⁵, Mark D P Willcox⁶

Affiliations

¹ Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India. Electronic address: ditixa.desai@gmail.com.
² Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
³ Centre for Ocular Research & Education (CORE), School of Optometry and Vision Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
⁴ Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India; L.M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat 380009, India.
⁵ Department of Chemical Engineering and Department of Anesthesiology, University of Florida, Gainesville, FL 32611, USA.
⁶ School of Optometry and Vision, University of New South Wales, Sydney, New South Wales 2052, Australia.

PMID: 34952149
DOI: 10.1016/j.ijpharm.2021.121414

Abstract

Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.

Keywords: Animal studies; Cyclosporine; Graphene oxide; Hydrogel contact lenses.

MeSH terms

Animals
Contact Lenses*
Cyclosporine
Graphite*
Hydrogels
Rabbits

Substances

Hydrogels
graphene oxide
Graphite
Cyclosporine