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Controlled non-invasive iontophoretic delivery of triamcinolone acetonide amino acid ester prodrugs into the posterior segment of the eye.
Eur J Pharm Biopharm. 2018 Nov; 132:157-167.EJ

Abstract

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.

Authors+Show Affiliations

School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, CMU-1, rue Michel Servet, 1211 Geneva 4, Switzerland.School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, CMU-1, rue Michel Servet, 1211 Geneva 4, Switzerland.School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, CMU-1, rue Michel Servet, 1211 Geneva 4, Switzerland. Electronic address: Yogi.Kalia@unige.ch.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

30266666

Citation

Santer, Verena, et al. "Controlled Non-invasive Iontophoretic Delivery of Triamcinolone Acetonide Amino Acid Ester Prodrugs Into the Posterior Segment of the Eye." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 132, 2018, pp. 157-167.
Santer V, Chen Y, Kalia YN. Controlled non-invasive iontophoretic delivery of triamcinolone acetonide amino acid ester prodrugs into the posterior segment of the eye. Eur J Pharm Biopharm. 2018;132:157-167.
Santer, V., Chen, Y., & Kalia, Y. N. (2018). Controlled non-invasive iontophoretic delivery of triamcinolone acetonide amino acid ester prodrugs into the posterior segment of the eye. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 132, 157-167. https://doi.org/10.1016/j.ejpb.2018.09.020
Santer V, Chen Y, Kalia YN. Controlled Non-invasive Iontophoretic Delivery of Triamcinolone Acetonide Amino Acid Ester Prodrugs Into the Posterior Segment of the Eye. Eur J Pharm Biopharm. 2018;132:157-167. PubMed PMID: 30266666.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Controlled non-invasive iontophoretic delivery of triamcinolone acetonide amino acid ester prodrugs into the posterior segment of the eye. AU - Santer,Verena, AU - Chen,Yong, AU - Kalia,Yogeshvar N, Y1 - 2018/09/25/ PY - 2018/04/20/received PY - 2018/09/20/revised PY - 2018/09/24/accepted PY - 2018/9/30/pubmed PY - 2019/1/19/medline PY - 2018/9/30/entrez KW - Biodistribution KW - Eye globe KW - Posterior segment KW - Prodrugs KW - Transscleral iontophoresis KW - Triamcinolone acetonide SP - 157 EP - 167 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 132 N2 - 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. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/30266666/Controlled_non_invasive_iontophoretic_delivery_of_triamcinolone_acetonide_amino_acid_ester_prodrugs_into_the_posterior_segment_of_the_eye_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(18)30522-8 DB - PRIME DP - Unbound Medicine ER -