Characterization and evaluation of β-glucan formulations as injectable implants for protein and peptide delivery

Drug Dev Ind Pharm. 2012 Nov;38(11):1337-43. doi: 10.3109/03639045.2011.650646. Epub 2012 Feb 3.

Abstract

Context: Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature.

Objective: To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of β-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG.

Materials and methods: Oscillation viscometry was used to evaluate the gel character by measuring flow index (N), storage (G') and loss (G") moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells.

Results: Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly (p < 0.001) from 3.65 ± 0.43 to 34.30 ± 8.90 (dextran) and 805.80 ± 5.30 (PEG) 24 h after polymer addition. In vitro release profiles showed significantly (p < 0.05) reduced AUC(0-8 h), k and percentage of drug released from two-phase systems compared to β-glucan dispersions, with the PEG system resulting in the lowest amount released over 8 h (15.1 ± 1.6%).

Discussion: The unfavorable mixing enthalpy and higher water affinity of PEG resulted in the formation of a dense β-glucan gel.

Conclusion: 1.5% (w/w) β-glucan combined with PEG at a ratio of 1:3 seemed to be the most promising injectable formulation with respect to fastest gel formation, increased hardness and sustained release.

MeSH terms

  • Biocompatible Materials / chemistry*
  • Dextrans / chemistry
  • Drug Carriers / chemistry*
  • Drug Implants
  • Excipients / chemistry
  • Fluorescein / analysis
  • Gels
  • Hardness
  • Hydrogen-Ion Concentration
  • Models, Chemical
  • Peptides / administration & dosage*
  • Phase Transition
  • Polyethylene Glycols / chemistry
  • Proteins / administration & dosage*
  • Rheology
  • Solubility
  • Spectrometry, Fluorescence
  • Viscosity
  • beta-Glucans / chemistry*

Substances

  • Biocompatible Materials
  • Dextrans
  • Drug Carriers
  • Drug Implants
  • Excipients
  • Gels
  • Peptides
  • Proteins
  • beta-Glucans
  • Polyethylene Glycols
  • Fluorescein