In vivo distribution and ex vivo permeation of cyclosporine A prodrug aqueous formulations for ocular application.

Details

Serval ID
serval:BIB_C915B19F8A55
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In vivo distribution and ex vivo permeation of cyclosporine A prodrug aqueous formulations for ocular application.
Journal
Journal of Controlled Release : Official Journal of the Controlled Release Society
Author(s)
Rodriguez-Aller M., Guillarme D., El Sanharawi M., Behar-Cohen F., Veuthey J.L., Gurny R.
ISSN
1873-4995 (Electronic)
ISSN-L
0168-3659
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
170
Number
1
Pages
153-159
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Cyclosporine A is a poorly water-soluble, immunosuppressive drug used to treat a variety of ocular diseases. Its limited solubility makes challenging the development of a cyclosporine A-based eye drop for ocular topical application. Based on the prodrug strategy, the practically insoluble cyclosporine A was converted into a freely soluble prodrug. Such a water-soluble prodrug made it possible to develop water-based concentrated eye drops. The prodrug formulations were tested for their ex vivo permeation and in vivo distribution at three concentrations (equivalent to 0.05%, 0.50% and 2.00% w/v cyclosporine A). The ex vivo permeation experiments were performed on corneal and conjunctival epithelia. The in vivo distribution evaluated the total cyclosporine A present in the ocular structures as well as in serum, spleen and cervical lymphatic ganglions. Each prodrug formulation was compared to conventionally used cyclosporine A eye drops at an equivalent concentration. The experimental results showed that the tested eye drops behaved differently. The prodrug formulation was characterized by the following: i) preferential conjunctival penetration, ii) an interesting capacity to create large tissue deposits and iii) a lower risk of systemic complications and immunosuppression. The prodrug aqueous eye drop was demonstrated to be a patient-friendly option for the treatment of ocular diseases requiring high ocular levels of cyclosporine A, pushing the boundaries of the current therapeutic arsenal.
Pubmed
Web of science
Create date
19/08/2013 14:59
Last modification date
20/08/2019 15:44
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