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ACS Appl Bio Mater. 2020 Mar 16;3(3):1722-1729. doi: 10.1021/acsabm.0c00027. Epub 2020 Feb 25.

Size-Exclusive Nanoporous Biodegradable PLGA Capsules for Drug Delivery Implants and In Vivo Stability in the Posterior Segment.

ACS applied bio materials

Xingyu He, Zheng Yuan, Winston Kao, Daniel Miller, S Kevin Li, Yoonjee C Park

Affiliations

  1. Cincinnati Eye Institute, Cincinnati, Ohio 45242, United States.
  2. College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45221, United States.

PMID: 35021661 DOI: 10.1021/acsabm.0c00027

Abstract

The current standard of care for posterior segment eye diseases, such as neovascular age-related macular degeneration, diabetic macular edema, is frequent intravitreal injections or sustained-release drug implants. Intravitreal injections have a low incidence of serious complications such as retinal detachment, endophthalmitis, iatrogenic traumatic cataract, or iridocyclitis and injection-site reactions. However, there is a significant burden to the patient, the patient's family, and the health system because current intravitreal therapies require between every 4 and 12 week administration over many years. Drug implants have side effects due to the burst release of the drugs, and their release cannot be easily controlled after implantation. We have developed a size-exclusive nanoporous biodegradable PLGA capsule for dosage-controllable drug delivery implants. We have optimized the nanoporous structure by tuning the ratio between porogen and high molecular weight PLGA and tested the stability against passive leakage of the liposomal drug (1-2 μm) and the safety in vivo rabbit eyes for 6 months. Our results suggest that PLGA implants made of the nanoporous PLGA sheet can selectively release drug molecules, keeping the liposomal drug inside. In addition, the implant was biocompatible, causing no inflammation and foreign body response when implanted for 6 months. Overall, the implant shows great potential for on-demand dose-controllable drug release applications.

Keywords: biodegradable PLGA implants; drug delivery; in vivo stability; nanoporous PLGA sheets; posterior segment

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