Drug tissue distribution of tudca from a biodegradable suprachoroidal implant versus intravitreal or systemic delivery in the pig model

Timothy W. Olsen, Roy B. Dyer, Fukutaro Mano, Jeffrey H. Boatright, Micah A. Chrenek, Daniel Paley, Kathy Wabner, Jenn Schmit, Ju Byung Chae, Jana T. Sellers, Ravinder J. Singh, Timothy S. Wiedmann

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To determine local ocular tissue levels of the bile acid, tauroursodeoxycholic acid (TUDCA), in the pig model using oral, intravenous (IV), intravitreal injection (IVitI) and low- and high-dose suprachoroidal, sustained-release implants (SCI-L or SCI-H). Methods: Forty-six pigs (92 globes) were included in the study. TUDCA was delivered orally in 5 pigs, IV in 4, IVitI in 6, SCI-L in 17, and SCI-H in Testing timeframes varied from the same day (within minutes) for IV; 1 to 6 days, oral; and 1 to 4 weeks, IVitI and SCI. Enucleated globes were dissected, specimens from specific tissues were separated, and TUDCA was extracted and quantified using mass spectrometry. Results: The highest TUDCA tissue levels occurred after IV delivery in themacula (252} 238 nM) and peripheral retina (196 } 171 nM). Macular choroid and peripheral choroid levels were also high (1032} 1269 and 1219 } 1486 nM, respectively). For IVitI delivery, macular levels at day 6 were low (0.5 } 0.5 nM), whereas peripheral choroid was higher (15.3 } 16.7 nM). Neither the SCI-L nor SCI-H implants delivered meaningful macular doses (≤1 nM); however, peripheral retina and choroid levels were significantly higher. Bile acid isoforms were found in the serum specimens. Conclusions: The highest TUDCA tissue levels in the pig model were obtained using IV delivery. Oral delivery was associated with reasonable tissue levels. Local delivery (IVitI and SCI) was able to achieve measurable local ocular tissue levels. Translational Relevance: Diffusional kinetics from the suprachoroidal space follow the choroidal blood flow, away from the macula and toward the periphery.

Original languageEnglish (US)
Article number11
JournalTranslational Vision Science and Technology
Volume9
Issue number6
DOIs
StatePublished - May 2020

Bibliographical note

Funding Information:
Supported by the Emory University School of Medicine; Abraham J. & Phyllis Katz Foundation, Shenandoah, Georgia; unrestricted grant from Research to Prevent Blindness, New York; Chungbuk National University; and the National Institutes of Health/National Eye Institute Core Grant P30 EY006360. The sponsor or funding organization had no role in the design or conduct of this research.

Keywords

  • Bile acid
  • Drug delivery
  • Pharmacokinetics
  • Retinal degeneration

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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