Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 536, Issue 1, Pages 292-300Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2017.11.069
Keywords
Aciclovir; Herpes simplex; Transcorneal; Transscleral; Iontophoresis; Anterior segment; Posterior segment
Categories
Funding
- University of Geneva
- Fondation Ernst and Lucie Schmidheiny
- Societe Academique de Geneve
- China Scholarship Council
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The objective was to investigate (trans) corneal and transscleral iontophoresis of biolabile amino acid ester prodrugs of aciclovir (ACV-X, X= Arg, Gly and Trp) as a means to increase ocular bioavailability of ACV. Prodrugs displayed tissue-dependent susceptibility to hydrolysis. Iontophoresis of ACV-Arg, ACV-Gly and ACVTrp (5 mM, 0.5 mA/cm(2)) for 5 min followed by 55 min passive diffusion resulted in appreciable corneal deposition (21.5 +/- 5.1, 14.1 +/- 2.0 and 5.3 +/- 0.6 nmol/cm(2), respectively) and transcorneal permeation (13.9 +/- 1.6, 10.9 +/- 1.8 and 5.7 +/- 0.5 nmol/cm(2), respectively) of ACV species. In contrast, passive delivery of ACV across porcine cornea after 1 h was < LOQ (i.e.< 0.125 nmol/cm(2)). Transscleral permeation of ACV-Arg, ACV-Gly and ACV-Trp (9 mM, 1.25 mA/cm(2)) after iontophoresis for 5 min was 20.4 +/- 3.8, 12.3 +/- 0.3 and 8.4 +/- 0.4 nmol/cm(2), respectively - far superior to passive delivery which was again < LOQ. Using intact porcine eye globes, 5 min transscleral iontophoresis of ACV-Gly at 3.75 mA/cm(2) resulted in considerable delivery of ACV species to the choroid/retina and vitreous humour (5.7 +/- 2.3 and 11.7 +/- 3.7 nmol/cm(2), respectively). Furthermore, the average concentration of ACV species in the whole eyeball (4.5 +/- 1.6 nmol/cm(3)) was significantly higher than the IC50 of ACV against HSV-1 (< 0.22 nmol/cm(3)), demonstrating the potential application for the treatment of ocular HSV infections.
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