Effect of nano-encapsulation using human serum albumin on anti-angiogenesis activity of bevacizumab to target corneal neovascularization: Development, optimization and in vitro assessment

Abstract

Majorly in ocular neovascular diseases or corneal neovascularization, the up-regulation of vascular endothelial growth factor level has been observed. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits VEGF binding to its surface receptors. Intravitreal injections of anti-VEGF are the revolutionized treatment but, the weak point is the frequent injections to the eye site and which may lead to several complications. Hence, the current study aimed to assess the effect of nano-encapsulation using human serum albumin on the anti-angiogenesis activity of bevacizumab to target corneal neovascularization. Human serum albumin encapsulated bevacizumab nanoparticles were fabricated by the double emulsion solvent evaporation method. Screening and optimization of designed nanoparticles were carried out by using design of experiment (DoE) software. Optimized nanoparticles were characterized for various characteristics like FT-IR, size of the particles, polydispersity index, zeta potential, percentage of drug entrapment, SEM, TEM, XRD, DSC, drug release, drug release kinetics, drug permeation, ocular irritation (HET-CAM assay), histopathological study, and stability study. The compatibility between the components was confirmed by FT-IR and DSC studies. The average size of the nanoparticles was within the acceptable range. The entrapment efficiency was high and followed Korsmeyers-Peppas drug release kinetics. Transcorneal permeation of the drug was assessed by goat cornea. The SEM images showed nanoparticles were crystal type of structures with rough surfaces and spherical shapes of particles confirmed by TEM studies. HET-CAM assay disclosed that the formulation was safe to use and well-tolerated. Histopathological studies on goat cornea revealed no corneal tissue damage. Stability studies exhibited that the prepared nanoparticle formulation was stable in accelerated storage conditions. Thus, the currently designed novel formulation could increase the bioavailability and decrease the toxicity of bevacizumab during corneal neovascularization therapy. Overall, applications of this nano technique in drug delivery systems promise further opportunities for the future.