A sustained dual drug delivery system for proliferative vitreoretinopathy

Ying Xiao; Kyung Seek Choi; David Warther; Kristyn Huffman; Stephanie Landeros; William R. Freeman; Michael J. Sailor; Lingyun Cheng

doi:10.1080/10717544.2020.1833382

Drug Delivery (Jan 2020)

A sustained dual drug delivery system for proliferative vitreoretinopathy

Ying Xiao,
Kyung Seek Choi,
David Warther,
Kristyn Huffman,
Stephanie Landeros,
William R. Freeman,
Michael J. Sailor,
Lingyun Cheng

Affiliations

Ying Xiao: Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Institute, University of California San Diego
Kyung Seek Choi: Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Institute, University of California San Diego
David Warther: Department of Chemistry and Biochemistry, University of California San Diego
Kristyn Huffman: Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Institute, University of California San Diego
Stephanie Landeros: Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Institute, University of California San Diego
William R. Freeman: Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Institute, University of California San Diego
Michael J. Sailor: Department of Chemistry and Biochemistry, University of California San Diego
Lingyun Cheng: Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Institute, University of California San Diego

DOI: https://doi.org/10.1080/10717544.2020.1833382
Journal volume & issue: Vol. 27, no. 1
pp. 1461 – 1473

Abstract

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Proliferative vitreoretinopathy (PVR) is a significant threat for vision recovery from retinal detachment or ocular trauma. Currently, no approved pharmacological intervention to prevent PVR. Daunorubicin (DNR) and dexamethasone (DEX) were sequentially loaded into oxidized porous silicon (pSiO2) particles by covalent conjugation. The DNR + DEX-loaded particles, and control particles loaded with DNR only and DEX only were incubated with RPE-populated collagen for daily gel surface quantitation. Toxicity was monitored by ophthalmic examinations and histological evaluation 21 days after injection. At 3rd week following intravitreal injection, a localized retinal detachment (RD) was created by subretinal injection of Healon in all pretreated eyes in addition to 3 non-interventional control eyes. 10 µg of bromodeoxyuridine (BrdU) was injected into the vitreous 4 h before sacrifice on day 3 after RD induction. Retinal sections were stained for glial fibrillary green protein (GFAP) and BrdU to identify activated glial cells and retinal cell proliferation. The studies demonstrated that all three pSiO2 particle types were well tolerated in vivo. DNR alone and DNR + DEX combination formulations demonstrated equally strong suppression on gel contraction (least square mean area of the gel: control = 1.71 vs. 30DNR = 1.85 or 30/40Dual = 1.83, p < .05). Eyes pretreated with pSiO2−DNR + DEX exhibited the least GFAP activation (least square mean intensity mm−2: Dual = 4.03, DNR = 7.76, Dex = 16.23, control = 29.11, p < .05) and BrdU expression (Mean number of BrdU positive cells per mm of retina: Dual = 2.77, DNR = 4.58, Dex = 4.01, control = 6.16, p < .05). The synergistic effect of a sustained release pSiO2−DNR/DEX showed promise for the prevention of PVR development while reducing the necessary therapeutic concentration of each drug.

Published in Drug Delivery

ISSN: 1071-7544 (Print); 1521-0464 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.tandfonline.com/journals/idrd

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