Citric acid crosslinked carboxymethylcellulose-poly(ethylene glycol) hydrogel films for delivery of poorly soluble drugs

Int J Biol Macromol. 2018 Oct 15;118(Pt A):783-791. doi: 10.1016/j.ijbiomac.2018.06.142. Epub 2018 Jun 28.

Abstract

In present work, carboxymethylcellulose (CMC) - polyethylene glycol (PEG) hydrogel films were prepared using citric acid as a non-toxic crosslinking agent, for the controlled delivery of model hydrophobic drug (ketoconazole). The carboxyl content of the hydrogel films were determined by acid-base titration. The films were characterized by solid state 13C NMR, ATR-FTIR, TGA and DSC, and evaluated for swelling behavior, drug loading, drug release, hemocompatibility, in vitro cytotoxicity and implantation test. An increase in the amount of PEG caused increase in the carboxyl content and swellability of the hydrogel films. The solid state 13C NMR, ATR-FTIR and thermal analysis confirmed the formation of ester crosslinks in between CMC and PEG in the hydrogel films. The release of KTZ was found to be retarded due to presence of grafted PEG in the hydrogel films. The hydrogel films exhibited excellent hemocompatibility and cytocompatibility. Implantation test revealed that the hydrogel films caused minimum inflammation. From the overall results, citric acid crosslinked CMC-PEG hydrogel films were found to be suitable for enhanced loading and controlled release of the poorly soluble drugs.

Keywords: Carboxymethylcellulose; Citric acid; Controlled release; Hydrogel films; Hydrophobic drugs; Poly (ethylene glycol).

MeSH terms

  • Animals
  • Carboxymethylcellulose Sodium* / chemistry
  • Carboxymethylcellulose Sodium* / pharmacology
  • Cell Line
  • Citric Acid / chemistry*
  • Cross-Linking Reagents / chemistry*
  • Drug Delivery Systems / methods*
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Ketoconazole* / chemistry
  • Ketoconazole* / pharmacology
  • Mice
  • Polyethylene Glycols* / chemistry
  • Polyethylene Glycols* / pharmacology

Substances

  • Cross-Linking Reagents
  • Hydrogels
  • Citric Acid
  • Polyethylene Glycols
  • Carboxymethylcellulose Sodium
  • Ketoconazole