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

Biol Pharm Bull. 2017;40(2):145-150. doi: 10.1248/bpb.b16-00437.

Abstract

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.

MeSH terms

  • Biosimilar Pharmaceuticals / administration & dosage
  • Biosimilar Pharmaceuticals / metabolism*
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / metabolism
  • Drug Carriers / administration & dosage
  • Drug Carriers / metabolism
  • Drug Delivery Systems / methods*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lactic Acid / administration & dosage
  • Lactic Acid / metabolism*
  • Microspheres*
  • Polyglycolic Acid / administration & dosage
  • Polyglycolic Acid / metabolism*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Ranibizumab / administration & dosage
  • Ranibizumab / metabolism*
  • Vascular Endothelial Growth Factor A / administration & dosage
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Biosimilar Pharmaceuticals
  • Delayed-Action Preparations
  • Drug Carriers
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Ranibizumab