Utilizing an Ex Vivo Skin Penetration Analysis Model for Predicting Ocular Drug Penetration: A Feasibility Study with Curcumin Formulations
Christian Raab,
Stefan Brugger,
Jara-Sophie Lechner,
Geisa Nascimento Barbalho,
Taís Gratieri,
Priyanka Agarwal,
Ilva D. Rupenthal,
Cornelia M. Keck
Affiliations
Christian Raab
Department of Pharmaceutics and Biopharmaceutics, Philipps-Universität Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany
Stefan Brugger
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa-New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand
Jara-Sophie Lechner
Department of Pharmaceutics and Biopharmaceutics, Philipps-Universität Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany
Geisa Nascimento Barbalho
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa-New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand
Taís Gratieri
Laboratory of Food, Drugs and Cosmetics (LTMAC), University of Brasilia, Brasilia 70910-900, Brazil
Priyanka Agarwal
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa-New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand
Ilva D. Rupenthal
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa-New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand
Cornelia M. Keck
Laboratory of Food, Drugs and Cosmetics (LTMAC), University of Brasilia, Brasilia 70910-900, Brazil
Objective: This study aimed to investigate the feasibility of using the digital image processing technique, developed to semi-quantitatively study dermal penetration, to study corneal penetration in an ex vivo porcine eye model. Here, we investigated various formulation strategies intended to enhance dermal and corneal bioavailability of the model hydrophobic drug, curcumin. Methods: Several formulation principles were explored, including oily solutions, oily suspensions, aqueous nanosuspension, micelles, liposomes and cyclodextrins. The dermal penetration efficacy was tested using an ex vivo porcine ear model previously developed at Philipps-Universität Marburg with subsequent digital image processing. This image analysis method was further applied to study corneal penetration using an ex vivo porcine whole-eye model. Results: For dermal penetration, oily solutions, oily suspensions and nanosuspensions exhibited the least penetration, whereas liposomes and cyclodextrins showed enhanced penetration. Corneal curcumin penetration correlated with dermal penetration, with curcumin loaded into cyclodextrins penetrating the deepest. Conclusions: Overall, our study suggests that the image analysis method previously developed for ex vivo skin penetration can easily be repurposed to study corneal penetration of hydrophobic drugs.