Details

Autor(en) / Beteiligte

• Santer, Verena
• Chen, Yong
• Kalia, Yogeshvar N.

Titel

Controlled non-invasive iontophoretic delivery of triamcinolone acetonide amino acid ester prodrugs into the posterior segment of the eye

Ist Teil von

• European journal of pharmaceutics and biopharmaceutics, 2018-11, Vol.132, p.157-167

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] This study investigated short duration transscleral iontophoretic delivery of four triamcinolone acetonide (TA) amino acid ester prodrugs (TA-AA) (alanine, Ala; arginine, Arg; isoleucine, Ile and lysine, Lys) using whole porcine eyes globes in vitro. Post-iontophoretic biodistribution of TA was quantified by UHPLC-MS/MS in the different ocular compartments (cornea, aqueous humor, sclera, ciliary body, choroid and retinal pigmented epithelium (RPE), neural retina and vitreous humor). Transscleral iontophoresis (3 mA/cm2 for 10 min) increased total drug delivery of the TA-AA prodrugs by 14-30-fold as compared to passive diffusion. The TA-AA prodrugs had distinct biodistribution profiles – the penetration depth achieved was dependent on their physicochemical properties (e.g. lipophilicity for TA-Ile) and susceptibility to hydrolysis (e.g. TA-Arg). Intraocular drug distribution was also influenced by prodrug binding to melanin (TA-Lys). Interestingly, under conditions of equivalent charge (6 mA/cm2 for 5 min vs. 1.5 mA/cm2 for 20 min, i.e. 1.44 C respectively) the longer duration (20 min) at lower current density resulted in ∼6 times more TA delivery into the vitreous humor. Overall, the study provided further evidence of the potential of transscleral iontophoresis for the non-invasive treatment of posterior segment inflammatory diseases.