Self-aggregates of 3,6-O,O'-dimyristoylchitosan derivative are effective in enhancing the solubility and intestinal permeability of camptothecin

Carbohydr Polym. 2017 Dec 1;177:178-186. doi: 10.1016/j.carbpol.2017.08.114. Epub 2017 Aug 31.

Abstract

The aim of this work was to investigate the potential of a new 3,6-O,O'-dimyristoyl derivative amphiphilic chitosan (DMCh), in improving the solubility of camptothecin (CPT), a hydrophobic anticancer drug, and its potential oral delivery. FTIR, 1H NMR and solid-state 13C NMR spectroscopy were used to characterize DMCh and to determine its average degree of substitution (DS¯=6.8%). DMCh/CPT micelles size ranged from (281-357nm), zeta potential (+32-50mV) of encapsulation efficiency of 42-100%. The in vitro cell viability showed that DMCh/CPT micelles were able to reduce the toxicity of CPT. The in vitro permeability of CPT through Caco-2 and Caco-2/HT29-MTX intestinal models was increased up to ten fold when formulated into DMCh micelles, underlining the mucoadhesive properties of the nanocarrier. DMCh/CPT micelles are able to enhance CPT solubility and bioavailability while reduce its cytotoxicity, showing the great potential for intestinal delivery of hydrophobic drugs.

Keywords: Amphiphilic chitosan derivative; Camptothecin; Chitosan; Oral drug delivery; Polymeric micelles.

MeSH terms

  • Caco-2 Cells
  • Camptothecin / administration & dosage
  • Camptothecin / chemistry
  • Camptothecin / metabolism*
  • Chitosan / chemistry*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology*
  • Humans
  • Micelles
  • Particle Size
  • Permeability / drug effects
  • Solubility

Substances

  • Drug Carriers
  • Micelles
  • Chitosan
  • Camptothecin