Polyionic complexes of chitosan-N-arginine with alginate as pH responsive and mucoadhesive particles for oral drug delivery applications

Int J Biol Macromol. 2020 Apr 1:148:550-564. doi: 10.1016/j.ijbiomac.2020.01.160. Epub 2020 Jan 17.

Abstract

The production of efficient micro and nanoparticles of pH-responsive and mucoadhesive properties is of high scrutiny. We produced a drug carrier bioparticle providing such structural features. Thereby, protonated chitosan bearing chemically bonded arginine was interacted with ionized alginate, leading to the assembling of colloidal particles of specific characteristics. Ideally, the ratio of chitosan-arginine monomers to alginate monomer is 1.6 when the biopolymers are highly charged, providing electrostatic interaction with Gibbs energy compensation around -14 kcal/mol. Both size and surface charge of the bioparticle respond to pH variation, leading to structures of nano to micro hydrodynamic diameters and of positive, nearly neutral and negative zeta potential, with nanoscopic structure changing from mass to surface fractals. The inclusion of two hydrophobic model drugs provided some specific physicochemical features. Following freeze-drying, the bioparticles present both irregular shape and surface morphology, but an overall similar dry structure. An in vivo study of oral administration to teleost fish revealed that the bioparticles attain the intestine mucus and further, the interaction with the intestinal mucosa is timely dependent thanks to the mucoadhesive property. The in vivo study endorsed that the bioparticle provides high compliance to freshwater ornamental fish, highlighting it as a material of promising application.

Keywords: Biomaterial; Biopolymers; Chitosan-arginine; In vivo application; Structure.

MeSH terms

  • Alginates / chemistry*
  • Algorithms
  • Animals
  • Biopolymers / chemistry
  • Chitosan / chemistry*
  • Drug Carriers* / chemistry
  • Drug Delivery Systems*
  • Fishes
  • Hydrogen-Ion Concentration*
  • Ions*
  • Models, Chemical
  • Molecular Structure
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Spectrum Analysis
  • Thermodynamics

Substances

  • Alginates
  • Biopolymers
  • Drug Carriers
  • Ions
  • Chitosan