Optimizing electrostatic interactions for controlling the release of proteins from anionic and cationically modified alginate

Eur J Pharm Biopharm. 2017 Aug:117:232-243. doi: 10.1016/j.ejpb.2017.04.025. Epub 2017 Apr 27.

Abstract

Alginate and cationically modified alginate microparticles were prepared with the goal of developing hydrogel microparticles that offer controlled release of protein drugs mainly by modification of the absolute charge of the hydrogel network. Protein loading and release studies were carried out using model proteins with different net charges (i.e. low, high, and neutral isoelectric points) covering a broad range of molecular weights. The Projection to Latent Structures (PLS) method was used for qualitatively and quantitatively describing the relationships between the properties of proteins such as net charge and molecular weight, polymer properties including degree of substitution and microparticle size, and the release kinetics (ktn). It was found that electrostatic interactions and protein molecular weight had the greatest impact on parameter k while parameter n was mostly affected by polymer and buffer properties. In addition to understanding the current trends, the multivariate statistical method also provided an effective and reliable model as a beneficial tool for predicting and optimizing protein delivery systems.

Keywords: Alginate; Controlled release; Electrostatic interactions; Hydrogel microparticles; Multivariate statistical analysis; Protein delivery.

MeSH terms

  • Alginates / chemistry
  • Alginates / metabolism*
  • Animals
  • Anions
  • Cations
  • Cattle
  • Chymotrypsin / chemistry
  • Chymotrypsin / metabolism
  • Drug Delivery Systems / methods*
  • Drug Liberation*
  • Glucuronic Acid / chemistry
  • Glucuronic Acid / metabolism
  • Hexuronic Acids / chemistry
  • Hexuronic Acids / metabolism
  • Insulin / chemistry
  • Insulin / metabolism
  • Serum Albumin, Bovine / chemistry
  • Serum Albumin, Bovine / metabolism*
  • Static Electricity*

Substances

  • Alginates
  • Anions
  • Cations
  • Hexuronic Acids
  • Insulin
  • Serum Albumin, Bovine
  • Glucuronic Acid
  • Chymotrypsin