pH-responsive hydrogels with dispersed hydrophobic nanoparticles for the oral delivery of chemotherapeutics

J Biomed Mater Res A. 2013 Aug;101(8):2229-36. doi: 10.1002/jbm.a.34532. Epub 2012 Dec 28.

Abstract

Amphiphilic polymer carriers were formed by polymerizing a hydrophilic, pH-responsive hydrogel composed of poly(methacrylic-grafted-ethylene glycol) (P(MAA-g-EG)) in the presence of hydrophobic PMMA nanoparticles. These polymer carriers were varied in PMMA nanoparticle content to elicit a variety of physiochemical properties which would preferentially load doxorubicin, a hydrophobic chemotherapeutic, and release doxorubicin locally in the colon for the treatment of colon cancers. Loading levels ranged from 49% to 64% and increased with increasing nanoparticle content. Doxorubicin loaded polymers were released in a physiological model where low pH was used to simulate the stomach and then stepped to more neutral conditions to simulate the upper small intestine. P(MAA-g-EG) containing nanoparticles were less mucoadhesive as determined using a tensile tester, polymer samples, and fresh porcine small intestine. The cytocompatibility of the polymer materials were assessed using cell lines representing the GI tract and colon cancer and were noncytotoxic at varying concentrations and exposure times.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Cell Line
  • Cell Line, Tumor
  • Delayed-Action Preparations / chemistry*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Humans
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Intestine, Small / metabolism
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry*
  • Polymethacrylic Acids / chemistry*
  • Swine

Substances

  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Hydrogels
  • Polymethacrylic Acids
  • poly(methacrylic acid-ethylene glycol)
  • Polyethylene Glycols
  • Doxorubicin