Methotrexate loaded alginate microparticles and effect of Ca2+ post-crosslinking: An in vitro physicochemical and biological evaluation

Int J Biol Macromol. 2018 Apr 15:110:294-307. doi: 10.1016/j.ijbiomac.2017.10.148. Epub 2017 Oct 31.

Abstract

Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca2+. The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11μm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations.

Keywords: Alginate; Methotrexate; Microparticles.

MeSH terms

  • Alginates* / chemistry
  • Alginates* / pharmacokinetics
  • Alginates* / pharmacology
  • Animals
  • Calcium* / chemistry
  • Calcium* / pharmacokinetics
  • Calcium* / pharmacology
  • Cell Line
  • Cross-Linking Reagents / chemistry
  • Cross-Linking Reagents / pharmacokinetics
  • Cross-Linking Reagents / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Carriers* / pharmacology
  • Glucuronic Acid / chemistry
  • Glucuronic Acid / pharmacokinetics
  • Glucuronic Acid / pharmacology
  • Hexuronic Acids / chemistry
  • Hexuronic Acids / pharmacokinetics
  • Hexuronic Acids / pharmacology
  • Methotrexate* / chemistry
  • Methotrexate* / pharmacokinetics
  • Methotrexate* / pharmacology
  • Mice

Substances

  • Alginates
  • Cross-Linking Reagents
  • Drug Carriers
  • Hexuronic Acids
  • Glucuronic Acid
  • Calcium
  • Methotrexate