June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Sustained delivery of griseofulvin by polymeric microparticles for neovascular eye disease treatment
Author Affiliations & Notes
  • Dhawal Chobisa
    Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, United States
    IPDO, Innovation Plaza, Dr. Reddy's Laboratories, Hyderabad, Telangana, India
  • Kamakshi Sishtla
    Eugene and Marilyn Glick Eye Institute and Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Timothy William Corson
    Eugene and Marilyn Glick Eye Institute and Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Yoon Yeo
    Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, United States
    Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States
  • Footnotes
    Commercial Relationships   Dhawal Chobisa, Dr. Reddy's Laboratories (F), Dr. Reddy's Laboratories (E); Kamakshi Sishtla, None; Timothy Corson, 15/009,339; 62/837,506 (P); Yoon Yeo, None
  • Footnotes
    Support  Dr. Reddy’s Laboratories-Purdue University fellowship
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 199. doi:
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      Dhawal Chobisa, Kamakshi Sishtla, Timothy William Corson, Yoon Yeo; Sustained delivery of griseofulvin by polymeric microparticles for neovascular eye disease treatment. Invest. Ophthalmol. Vis. Sci. 2021;62(8):199.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Current treatments for neovascular eye diseases based on anti-vascular endothelial growth factor therapy are ineffective in a significant fraction of patients. In seeking alternative therapeutic targets, ferrochelatase (FECH) has been identified as a promising protein. We set out to develop an injectable, long-acting microparticle (MP) formulation for sustained delivery of griseofulvin (GRF), which is metabolized into a FECH inhibitor.

Methods : GRF was loaded in poly(lactic-co-glycolic acid) (PLGA) MPs by the double emulsion (W1/O/W2) method. GRF and PLGA were added to the organic (O) phase, and magnesium hydroxide (Mg(OH)2) (0-20 wt%) was added to the internal aqueous (W1) phase. The effects of Mg(OH)2 content on particle size (laser diffraction), morphology (scanning electron microscopy), and in vitro release were evaluated. The sustained antiproliferative effect of MPs was evaluated on human retinal endothelial cells (HRECs) using an AlamarBlue assay.

Results : The mean particle size (D50) of MPs was measured to be in the range of 15-22 µm (Figure 1a). MPs were spherical with sizes consistent with the laser diffraction measurement. MPs prepared without Mg(OH)2 had a solid surface, whereas those with Mg(OH)2 showed porous surfaces. The porosity increased with the amount of Mg(OH)2 added to the MPs (Figure 1b). MPs without Mg(OH)2 released ~15% of loaded drug in phosphate-buffered saline (pH 7.4) with 0.2% Tween 80 at 37 °C in 1 day and slowly released the remainder (up to ~80%) in 60 days (Figure 2a). The inclusion of Mg(OH)2 dramatically changed the GRF release profile. MPs with 20% Mg(OH)2 showed a high burst release of GRF (~70%), followed by a complete release in 5 days. MPs with 10% and 5% Mg(OH)2 showed >90% and >75% drug release in 5 days. The MPs containing 2% Mg(OH)2 showed a minimal burst release (~18% in 1 day) followed by continuous release (~100% in 38 days) and were considered the most suitable for 1 month GRF delivery. GRF released from the MPs throughout the release period remained active and inhibited the proliferation of HRECs (Figure 2b).

Conclusions : GRF-loaded PLGA MP were developed for long-term ocular delivery. The optimized MP formulation provided a sustained release of bioactive GRF over a month and effectively inhibited proliferation of HRECs. These results warrant further evaluation in animal models to test the feasibility of neovascular eye disease treatment.

This is a 2021 ARVO Annual Meeting abstract.

 

 

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