These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Ex vivo models to evaluate the role of ocular melanin in trans-scleral drug delivery.
    Author: Pescina S, Santi P, Ferrari G, Padula C, Cavallini P, Govoni P, Nicoli S.
    Journal: Eur J Pharm Sci; 2012 Aug 15; 46(5):475-83. PubMed ID: 22484210.
    Abstract:
    Trans-scleral delivery is nowadays considered as a possible way to deliver drugs to the posterior segment of the eye. Despite the potentiality of this administration route, there is a lack of fundamental knowledge on the role of the numerous barriers involved. The aim of this work was to develop an easy and cheap ex vivo method to evaluate the barrier properties of the choroid-Bruch's layer and in particular to estimate the role of melanin in drug diffusion through ocular tissues. In vitro binding studies were performed to estimate drug affinity for melanin; model molecules used were methylene blue, propranolol, levofloxacin and methylprednisolone sodium succinate. The ex vivo model set up is based on porcine eye bulbs with light blue iris or brown iris. While the choroid of brown eyes is dark, the choroid of blue eyes is transparent, due to the absence of melanin. Permeation experiments using pigmented and not-pigmented porcine tissues gave the opportunity to discriminate between the barrier role of choroid-Bruch's membrane as such and the barrier role of melanin. Ex vivo permeation experiments can be performed using isolated choroid-Bruch's or the sclera-choroid-Bruch's layer. In this last case, it is possible to take into account also the barrier role of the sclera that tends to decrease the drug concentration at the sclera/choroid interface, thus amplifying the effect of melanin. The data obtained in this paper indicate that for some drugs melanin can really represent a barrier and the effect can imply a lower drug flux or simply a longer lag time depending on the kind of drug and the concentration applied. However, it is a saturable barrier, thus its effect can probably be overtaken by high doses or multiple administrations. The ex vivo model set up can help to refine computational models, to better evaluate the interplay among static, dynamic and metabolic barriers. Additionally, since human eyes display a full range of pigmentation, the model could also be useful to investigate the possible influence of pigmentation phenotype on trans-scleral delivery.
    [Abstract] [Full Text] [Related] [New Search]