Abstract
Purpose: :
To develop NPinPMP using supercritical fluid technology for sustained delivery of stable bevacizumab.
Methods: :
Using biodegradable poly(lactide-co-glycolide) family of polymers and supercritical carbon dioxide pressure quench technology, nanoparticles containing bevacizumab (NP) were loaded in porous microspheres (PMP). The prepared NPinPMP formulation was characterized for mean particle size, morphology (SEM and confocal microscopy), and in vitro release of bevacizumab in PBS pH 7.4 using ELISA. The stability of released bevacizumab was evaluated using size exclusion chromatography (SEC), circular dichorism (CD), and by SDS-PAGE. Further, in vivo delivery of bevacizumab was evaluated following intravitreal administration of Alexa Fluor conjugated bevacizumab in NPinPMP in a rat model. In vivo drug delivery was monitored using Fluorotron MasterTM.
Results: :
NPinPMP were of a mean size of 9.6 µm. The SEM and confocal images indicated incorporation of bevacizumab NP in PMP. The in vitro drug release was sustained for 4 months. Stability studies indicated the integrity of bevacizumab as a monomer. NPinPMP sustained intravitreal bevacizumab delivery to a greater extent than plain bevacizumab in the in vivo study.
Conclusions: :
Incorporation of bevacizumab NP in PMP allows sustained intravitreal delivery of the protein drug for 4 months.
Keywords: age-related macular degeneration • choroid: neovascularization • visual development