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Updated: May 9, 2026
Encapsulated Cell Technology for the Delivery of Biologics to the Mouse Eye
Published on: March 30, 2020
Long-term suppression of ocular neovascularization by intraocular injection of biodegradable polymeric particles
Ron B Shmueli1, Masayuki Ohnaka, Akiko Miki
1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Abstract:
Aberrant angiogenesis can cause or contribute to a number of diseases such as neovascular age-related macular degeneration (NVAMD). While current NVAMD treatments target angiogenesis, these treatments are not effective for all patients and also require frequent intravitreal injections. New agents and delivery systems to treat NVAMD could be beneficial to many patients. We have recently developed a serpin-derived peptide as an anti-angiogenic agent. Here, this peptide is investigated for activity in human retinal endothelial cells in vitro and for reducing angiogenesis in a laser-induced choroidal neovascularization mouse model of NVAMD in vivo. While frequent intravitreal injections can be tolerated clinically, reducing the number of injections can improve patient compliance, safety, and outcomes. To achieve this goal, and to maximize the in vivo activity of injected peptide, we have developed biodegradable polymers and controlled release particle formulations to extend anti-angiogenic therapy. To create these devices, the anionic peptides are first self-assembled into nanoparticles using a biodegradable cationic polymer and then as a second step, these nanoparticles are encapsulated into biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles. In situ, these particles show approximately zero-order, linear release of the anionic peptide over 200 days. These particles are made of safe, hydrolytically degradable polymers and have low endotoxin. Long-term in vivo experiments in the laser-induced neovascularization model for NVAMD show that these peptide-releasing particles decrease angiogenesis for at least fourteen weeks in vivo following a single particle dose and therefore are a promising treatment strategy for NVAMD.
Insights
A novel peptide effectively inhibits aberrant angiogenesis, a key factor in neovascular age-related macular degeneration (NVAMD). Biodegradable particles provide sustained, long-term release of this peptide, offering a promising new treatment strategy for NVAMD.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Pharmacology
Background:
- Aberrant angiogenesis contributes to diseases like neovascular age-related macular degeneration (NVAMD).
- Current NVAMD treatments targeting angiogenesis have limitations, including patient non-responsiveness and the need for frequent intravitreal injections.
- Developing novel anti-angiogenic agents and improved delivery systems is crucial for better NVAMD patient outcomes.
Purpose of the Study:
- To investigate the anti-angiogenic potential of a newly developed serpin-derived peptide.
- To evaluate the efficacy of biodegradable polymer-based controlled-release particles for delivering this peptide in an NVAMD mouse model.
- To assess the duration of therapeutic effect and patient compliance benefits of sustained peptide delivery.
Main Methods:
- In vitro studies using human retinal endothelial cells to assess peptide activity.
- In vivo evaluation in a laser-induced choroidal neovascularization mouse model to measure angiogenesis reduction.
- Development of biodegradable nanoparticles encapsulating the peptide within poly(lactic-co-glycolic acid) (PLGA) microparticles for controlled release.
Main Results:
- The serpin-derived peptide demonstrated anti-angiogenic activity in vitro.
- Biodegradable PLGA microparticles achieved approximately zero-order release of the peptide over 200 days.
- A single dose of these peptide-releasing particles significantly decreased angiogenesis in vivo for at least 14 weeks in the NVAMD mouse model.
Conclusions:
- The developed peptide is a potent anti-angiogenic agent.
- Biodegradable, controlled-release PLGA microparticle formulations offer a promising strategy for sustained NVAMD therapy.
- This approach has the potential to improve patient compliance and outcomes by reducing the frequency of intravitreal injections.
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