Photocrosslinking of dextran and polyaspartamide derivatives: a combination suitable for colon-specific drug delivery

J Control Release. 2007 Jun 22;119(3):328-38. doi: 10.1016/j.jconrel.2007.03.005. Epub 2007 Mar 15.

Abstract

The aim of this study was to prepare and characterize novel hydrogels with polysaccharide-polyaminoacid structure, able to undergo an enzymatic hydrolysis in the colon and potentially useful for treating inflammatory bowel diseases (IBD). Starting materials were methacrylated dextran (DEX-MA) and methacrylated alpha,beta-poly(N-2-hydroxyethyl)-dl-aspartamide (PHM). These polymers were photocrosslinked by exposure of their aqueous solutions at 313 nm without photoinitiators. Different samples, shaped as microparticles, were obtained as a function of polymer concentration and irradiation time. FT-IR analysis confirmed the occurrence of a co-crosslinking between DEX-MA and PHM in all experimental conditions. Size analysis evidenced a narrow particle distribution and swelling studies, performed in twice-distilled water and simulated gastrointestinal fluids, showed a good affinity of these hydrogels towards the aqueous medium. DEX-MA/PHM based hydrogels undergo a negligible chemical hydrolysis, whereas they are partially degraded by dextranase. In vitro biological assays showed cell compatibility of these samples. Beclomethasone dipropionate (BDP), a drug recently proposed for the treatment of IBD was entrapped into a DEX-MA/PHM based hydrogel and its release was evaluated in the absence or in the presence of dextranase. Obtained release profiles suggest the potential use of BDP loaded DEX-MA/PHM based hydrogels for the treatment of IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Beclomethasone / administration & dosage
  • Beclomethasone / chemistry
  • Caco-2 Cells
  • Cell Adhesion
  • Cell Survival / drug effects
  • Colon / drug effects*
  • Cross-Linking Reagents / adverse effects
  • Cross-Linking Reagents / chemistry*
  • Cross-Linking Reagents / radiation effects
  • Dextrans / adverse effects
  • Dextrans / chemistry*
  • Dextrans / radiation effects
  • Drug Carriers / adverse effects
  • Drug Carriers / chemistry*
  • Drug Carriers / radiation effects
  • Drug Compounding
  • Drug Stability
  • Humans
  • Hydrogels / adverse effects
  • Hydrogels / chemistry*
  • Hydrogels / radiation effects
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Methacrylates / adverse effects
  • Methacrylates / chemistry*
  • Methacrylates / radiation effects
  • Mucins / chemistry
  • Particle Size
  • Peptides / adverse effects
  • Peptides / chemistry*
  • Peptides / radiation effects
  • Photochemistry

Substances

  • Cross-Linking Reagents
  • Dextrans
  • Drug Carriers
  • Hydrogels
  • Methacrylates
  • Mucins
  • Peptides
  • alpha,beta-poly((2-hydroxyethyl)-aspartamide)
  • methacrylated dextran
  • Beclomethasone