Zinc ions coordinated carboxymethyl chitosan-hyaluronic acid microgel for pulmonary drug delivery

Int J Biol Macromol. 2021 Dec 15;193(Pt B):1043-1049. doi: 10.1016/j.ijbiomac.2021.11.088. Epub 2021 Nov 18.

Abstract

Microgel affords a porous and swollen microstructure for the establishment of pulmonary delivery system with sustained released properties. Here, we report a microgel (with the diameter around 4 μm) prepared with a precipitation method, synthesized by coordinating Zn2+ to the Schiff base cross-linked carboxymethyl chitosan and glycol split hyaluronate. The microgel has shown well swollen and pH sensitive behaviors, high safety and biocompatibility in vitro. Besides, the biomaterial could escape from macrophage phagocytosis, a key factor contribute to quick drug clearance in the lung after co-incubated with RAW 264.7 cells. In consist with this, the bovine serum albumin loaded in the microgel showed sustained release behavior in 24 h in vitro; meanwhile, the drug had a retention time up to 36 h in the lung and followed by clearance in ICR mice through pulmonary administration. Thus, our microgel platform provides a promising candidate for pulmonary drug delivery systems with controlled release rate.

Keywords: Carboxymethyl chitosan; Hyaluronate; Microgel.

MeSH terms

  • Animals
  • Chitosan / analogs & derivatives*
  • Chitosan / chemistry
  • Chitosan / pharmacokinetics
  • Chitosan / pharmacology
  • Drug Carriers* / chemical synthesis
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Carriers* / pharmacology
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacokinetics
  • Hyaluronic Acid* / pharmacology
  • Lung / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Microgels / chemistry*
  • NIH 3T3 Cells
  • RAW 264.7 Cells
  • Zinc* / chemistry
  • Zinc* / pharmacokinetics
  • Zinc* / pharmacology

Substances

  • Drug Carriers
  • Microgels
  • carboxymethyl-chitosan
  • Hyaluronic Acid
  • Chitosan
  • Zinc