TY - JOUR
T1 - Anisotropic poly(lactic-co-glycolic acid) microparticles enable sustained release of a peptide for long-term inhibition of ocular neovascularization
AU - Kim, Jayoung
AU - Lima e Silva, Raquel
AU - Shmueli, Ron B.
AU - Mirando, Adam C.
AU - Tzeng, Stephany Y.
AU - Pandey, Niranjan B.
AU - Ben-Akiva, Elana
AU - Popel, Aleksander S.
AU - Campochiaro, Peter A.
AU - Green, Jordan J.
N1 - Funding Information:
The authors thank the NIH for support including R21EY026148, R01EY028996, and F32CA210482 (to ACM). The authors also thank the Research to Prevent Blindness/Dr. H. James and Carole Free Catalyst Award for support. JK thanks Samsung for scholarship support. The authors thank Dr. Jiangxia Wang and the Wilmer Biostatistics Core Grant (EY01765) for statistical assistance.
Publisher Copyright:
© 2019 Acta Materialia Inc.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Anisotropic
KW - Anti-angiogenesis
KW - Diabetic macular edema
KW - Microparticle
KW - Neovascular age-related macular degeneration
KW - Peptide
KW - Poly(lactic-co-glycolic acid)
UR - http://www.scopus.com/inward/record.url?scp=85071096270&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2019.07.054
DO - 10.1016/j.actbio.2019.07.054
M3 - Article
C2 - 31374338
AN - SCOPUS:85071096270
SN - 1742-7061
VL - 97
SP - 451
EP - 460
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -