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Purdue University

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Small, Nov 08 2023, | https://doi.org/10.1002/smll.202306479 Long-Acting Microparticle Formulation of Griseofulvin for Ocular Neovascularization Therapy

Dhawal Chobisa ^1,2, Anbukkarasi Muniyandi ³, Kamakshi Sishtla ³, Timothy W Corson ³, Yoon Yeo ^1,4

¹Department of Industrial and Molecular Pharmaceutics, Purdue University, 575 West Stadium Avenue, West Lafayette, IN, 47907, USA.

²Integrated Product Development Organization, Innovation Plaza Dr. Reddy's Laboratories, Hyderabad, 500050, India.

³Departments of Pharmacology & Toxicology and Ophthalmology, Indiana University School of Medicine, 1160 West Michigan Street, Indianapolis, IN, 46202, USA.

⁴Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Dr., West Lafayette, IN, 47907, USA.

CORRESPONDING AUTHORS : Timothy W. Corson, Yoon Yeo

Abstract

Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults. nAMD is treated with biologics targeting vascular endothelial growth factor; however, many patients do not respond to the current therapy. Here, a small molecule drug, griseofulvin (GRF), is used due to its inhibitory effect on ferrochelatase, an enzyme important for choroidal neovascularization (CNV). For local and sustained delivery to the eyes, GRF is encapsulated in microparticles based on poly(lactide-co-glycolide) (PLGA), a biodegradable polymer with a track record in long-acting formulations. The GRF-loaded PLGA microparticles (GRF MPs) are designed for intravitreal application, considering constraints in size, drug loading content, and drug release kinetics. Magnesium hydroxide is co-encapsulated to enable sustained GRF release over >30 days in phosphate-buffered saline with Tween 80. Incubated in cell culture medium over 30 days, the GRF MPs and the released drug show antiangiogenic effects in retinal endothelial cells. A single intravitreal injection of MPs containing 0.18 µg GRF releases the drug over 6 weeks in vivo to inhibit the progression of laser-induced CNV in mice with no abnormality in the fundus and retina. Intravitreally administered GRF MPs prove effective in preventing CNV, providing proof-of-concept toward a novel, cost-effective nAMD therapy.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-09)
연구진국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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