Anisotropic poly(lactic-co-glycolic acid) microparticles enable sustained release of a peptide for long-term inhibition of ocular neovascularization.
Anisotropic
Anti-angiogenesis
Diabetic macular edema
Microparticle
Neovascular age-related macular degeneration
Peptide
Poly(lactic-co-glycolic acid)
Journal
Acta biomaterialia
ISSN: 1878-7568
Titre abrégé: Acta Biomater
Pays: England
ID NLM: 101233144
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
13
04
2019
revised:
21
06
2019
accepted:
29
07
2019
pubmed:
3
8
2019
medline:
18
8
2020
entrez:
3
8
2019
Statut:
ppublish
Résumé
Leading causes of vision loss include neovascular age-related macular degeneration (NVAMD) and macular edema (ME), which both require frequent intravitreal injections for treatment. A safe, poly(lactic-co-glycolic acid) (PLGA)-based biodegradable polymeric microparticle (MP) delivery system was developed that encapsulates and protects a biomimetic peptide from degradation, allows sustained intraocular release through polymer hydrolysis, and demonstrates a prolonged anti-angiogenic effect in vivo in three different NVAMD animal models (a laser-induced choroidal neovascularization mouse model, a rhoVEGF transgenic mouse model, and a Tet/opsin/VEGF transgenic mouse model) following intravitreal administration. The role of copolymer composition and microparticle shape was explored and 85:15 lactide-to-glycolide PLGA formed into ellipsoidal microparticles was found to be effective at inhibiting neovascularization for at least 16 weeks in vivo. Treatments were found to not only inhibit the growth of neovascularization, but also to cause regression of the neovasculature, reduce vascular leakage, and prevent exudative retinal detachment. These particulate devices are promising for the sustained release of biologics in the eye and may be useful for treating retinal diseases. STATEMENT OF SIGNIFICANCE: Devastating retinal diseases cause blindness in millions of people around the world. Current protein-based treatments have insufficient efficacy for many patients and also necessitate frequent intravitreal injections. Here, we demonstrate a new treatment consisting of a peptide encapsulated in biodegradable microparticles. We explore the effects of copolymer composition and physical shape of polymeric microparticles and find that both modulate peptide release. Efficacy of the treatment was validated in three different mouse models and the lead formulation was determined to be effective long-term, for at least 16 weeks in vivo, following a single injection. Treatments inhibited and regressed neovascularization as well as reduced vascular leakage. Anisotropic polymeric microparticles are promising for the sustained release of biologics in the eye.
Identifiants
pubmed: 31374338
pii: S1742-7061(19)30543-4
doi: 10.1016/j.actbio.2019.07.054
pmc: PMC6939309
mid: NIHMS1538259
pii:
doi:
Substances chimiques
Delayed-Action Preparations
0
Peptides
0
Polylactic Acid-Polyglycolic Acid Copolymer
1SIA8062RS
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
451-460Subventions
Organisme : NCI NIH HHS
ID : F32 CA210482
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY001765
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY028996
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY026148
Pays : United States
Informations de copyright
Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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