Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.
Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.
Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University.
Yusuke
Y
Tanetsugu
Tatsuaki
T
Tagami
Takayuki
T
Terukina
Takaya
T
Ogawa
Masato
M
Ohta
Tetsuya
T
Ozeki
D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000069579:Ranibizumab / Q000008:administration & dosage / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000378:metabolism*
D059451:Biosimilar Pharmaceuticals; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000069579:Ranibizumab