Biocompatible and mucoadhesive bacterial cellulose-g-poly(acrylic acid) hydrogels for oral protein delivery

Mol Pharm. 2014 Nov 3;11(11):4130-42. doi: 10.1021/mp5003015. Epub 2014 Oct 7.

Abstract

Stimuli-responsive bacterial cellulose-g-poly(acrylic acid) hydrogels were investigated for their potential use as an oral delivery system for proteins. These hydrogels were synthesized using electron beam irradiation without any cross-linking agents, thereby eliminating any potential toxic effects associated with cross-linkers. Bovine serum albumin (BSA), a model protein drug, was loaded into the hydrogels, and the release profile in simulated gastrointestinal fluids was investigated. Cumulative release of less than 10% in simulated gastric fluid (SGF) demonstrated the potential of these hydrogels to protect BSA from the acidic environment of the stomach. Subsequent conformational stability analyses of released BSA by SDS-PAGE, circular dichroism, and an esterase activity assay indicated that the structural integrity and bioactivity of BSA was maintained and preserved by the hydrogels. Furthermore, an increase in BSA penetration across intestinal mucosa tissue was observed in an ex vivo penetration experiment. Our fabricated hydrogels exhibited excellent cytocompatibility and showed no sign of toxicity, indicating the safety of these hydrogels for in vivo applications.

Keywords: bacterial cellulose; biocompatibility; electron beam; hydrogels; oral protein delivery; protein conformational stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry*
  • Adhesives / chemistry
  • Animals
  • Cattle
  • Cellulose / chemistry*
  • Circular Dichroism
  • Cross-Linking Reagents / metabolism
  • Drug Delivery Systems*
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Male
  • Mucus / metabolism*
  • Ophthalmic Solutions / chemistry
  • Rats
  • Rats, Wistar
  • Serum Albumin, Bovine / administration & dosage*
  • Serum Albumin, Bovine / chemistry*

Substances

  • Acrylic Resins
  • Adhesives
  • Cross-Linking Reagents
  • Hydrogels
  • Ophthalmic Solutions
  • Serum Albumin, Bovine
  • carbopol 940
  • Cellulose