Cell binding and penetration of quaternized chitosan derivatives

Chitosan (Ch) is an attractive biopolymer with multiple reactive groups. However it is poorly soluble at neutral pH. Quaternization improves its solubility and permits the development of various positively charged drug delivery systems. The aim of this work was to study the solubility, toxicity, cell binding, and penetration of 20 kDa chitosan with 9, 40, 58 and 98% of quaternary ammonium group substitution (ChQ1 to ChQ4 accordingly). We showed that ChQ with substitution degree >40% was soluble in a wide pH range. Unexpectedly ChQ2 and ChQ3 were more toxic to cells than Ch, ChQ1 and ChQ4. Higher toxicity of ChQ was found against macrophage like cell line RAW264.7 than against epithelial cells MiaPaCa-2. All ChQ, in contrast to unmodified Ch, easily bound and penetrated the cells with the highest uptake by ChQ4. Thus, quaternized chitosan derivatives can be used for biomedical applications.