Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform

• Published in: Biological & pharmaceutical bulletin 2017/02/01, Vol.40(2), pp.145-150
• Main Authors: Tanetsugu, Yusuke, Tagami, Tatsuaki, Terukina, Takayuki, Ogawa, Takaya, Ohta, Masato, Ozeki, Tetsuya
• Format: Article
• Language: English
• Subjects: Age; age-related macular degeneration (AMD); Angiogenesis; anti-vascular endothelial growth factor (VEGF) therapy; Biodegradability; Biodegradable materials; Biodegradation; biosimilar; Biosimilar Pharmaceuticals - administration & dosage; Biosimilar Pharmaceuticals - metabolism; Cell proliferation; controlled release; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - metabolism; Drug Carriers - administration & dosage; Drug Carriers - metabolism; Drug Delivery Systems - methods; Endothelial cells; Eye; Glycolic acid; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Immunotherapy; Lactic Acid - administration & dosage; Lactic Acid - metabolism; Macular degeneration; Microparticles; Microspheres; Molecular weight; Monoclonal antibodies; poly(lactic-co-glycolic acid) (PLGA); Polyglycolic Acid - administration & dosage; Polyglycolic Acid - metabolism; Polylactide-co-glycolide; Proteolysis; ranibizumab; Ranibizumab - administration & dosage; Ranibizumab - metabolism; Sustainability; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - administration & dosage; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b16-00437

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.