Chitosan grafted-poly(ethylene glycol) methacrylate nanoparticles as carrier for controlled release of bevacizumab

Mater Sci Eng C Mater Biol Appl. 2019 May:98:843-860. doi: 10.1016/j.msec.2019.01.036. Epub 2019 Jan 10.

Abstract

The aim of the present study is to obtain, for the first time, polymeric nanocarriers based on the chitosan grafted-poly(ethylene glycol) methacrylate derivative. The strategy involves the use of chitosan grafted-poly(ethylene glycol) methacrylate with high solubility in water, obtained via Michael addition, in order to prepare potentially non-toxic micro/nanoparticles (MNPs). By modifying chitosan, its solubility in aqueous media was improved. Micro/nanoparticles-based chitosan grafted-poly(ethylene glycol) methacrylate were obtained under mild condition, with good and controlled swelling properties in acetate buffer solution (ABS) and phosphate buffer solution (PBS). The technique selected for the preparation of the MNPs was a double crosslinking (ionic and covalent) process in reverse emulsion which provide the mechanical stability of the polymeric nanocarrier. The chitosan derivative and MNPs were thoroughly characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM). The Scanning Electron Microscopy photographs revealed that prepared MNPs have different diameters depending on the used stirring rate and polymer concentration. Nanoparticles potential as drug delivery system was analyzed by loading bevacizumab (BEV) a full-length monoclonal antibody. Also, the prepared particles were found suitable from the cytotoxicity and hemocompatibility point of view enabling their potential use as delivery system for the treatment of posterior segment of the eye conditions.

Keywords: Bevacizumab; Chitosan; Double cross-linking; Interpenetrating network; Micro/Nanoparticles; Ophthalmology; Poly(ethylene glycol) methacrylate.

MeSH terms

  • Animals
  • Bevacizumab / pharmacology*
  • Calorimetry, Differential Scanning
  • Cell Shape / drug effects
  • Chitosan / chemical synthesis
  • Chitosan / chemistry*
  • Delayed-Action Preparations / pharmacology
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Fluorescein / chemistry
  • Fluorescence
  • Hemolysis / drug effects
  • Humans
  • Kinetics
  • Methacrylates / chemical synthesis
  • Methacrylates / chemistry*
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Particle Size
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Rabbits
  • Spectroscopy, Fourier Transform Infrared
  • Static Electricity
  • Thermogravimetry
  • Toxicity Tests

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Methacrylates
  • polyethylene glycol methacrylate
  • Bevacizumab
  • Polyethylene Glycols
  • Chitosan
  • Fluorescein