Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization

Acta Biomater. 2014 Mar;10(3):1194-205. doi: 10.1016/j.actbio.2013.11.028. Epub 2013 Dec 7.

Abstract

Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres. All synthesized microspheres were spherical in shape, calibrated in the 300-500 μm range, swelled in phosphate-buffered saline (PBS) and easily injectable through a microcatheter. Hydrolytic degradation experiments performed in PBS at 37 °C showed that all of the formulations tested were totally degraded in less than 2 days. The resulting degradation products were a mixture of low-molecular-weight compounds (PEG, lactic and glycolic acids) and water-soluble polymethacrylate chains having molecular weights below the threshold for renal filtration of 50 kg mol(-1) for the microspheres containing MDO. Both the microspheres and the degradation products were determined to exhibit minimal cytotoxicity against L929 fibroblasts. Additionally, in vivo implantation in a subcutaneous rabbit model supported the in vitro results of a rapid degradation rate of microspheres and provided only a mild and transient inflammatory reaction comparable to that of the control group.

Keywords: Degradable; Embolization; Hydrolyzable crosslinker; Microsphere; PEG-based hydrogel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / drug effects*
  • Doxorubicin / pharmacology
  • Embolization, Therapeutic*
  • Hydrolysis
  • Implants, Experimental
  • Lactic Acid / chemical synthesis
  • Lactic Acid / chemistry
  • Lactic Acid / pharmacology
  • Methacrylates / chemical synthesis
  • Methacrylates / chemistry
  • Methacrylates / pharmacology*
  • Mice
  • Microspheres*
  • Molecular Weight
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology*
  • Polyglycolic Acid / chemical synthesis
  • Polyglycolic Acid / chemistry
  • Polyglycolic Acid / pharmacology
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rabbits
  • Spectroscopy, Fourier Transform Infrared
  • Subcutaneous Tissue / drug effects

Substances

  • Methacrylates
  • polyethylene glycol methacrylate
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols
  • Doxorubicin