Scheme 1.

In vivo toxicity evaluation of glycol chitosan nanoparticles (CNPs). A The CNPs were prepared by conjugating hydrophilic glycol chitosan with hydrophobic 5β-cholanic acid. B These CNPs have been widely studied for tumor-targeted delivery of various chemical drugs, such as paclitaxel (PTX), docetaxel (DTX), camptothecin (CPT), doxorubicin (DOX), cisplatin (CDDP), chlorin e6 (Ce6) and protoporphyrin IX (PpIX). C When the CNPs were intravenously injected into tumor models, although they can efficiently accumulate within the tumor tissues by EPR effect, tumor-targeting efficiency is less than 5% and considerable amount (> 95%) is non-specifically accumulated in the normal organs. The precise toxicological risks caused by these in vivo behaviors of CNPs have not been fully investigated at repeated high-dose condition; thus, we performed the in vivo toxicity evaluation for CNPs focused on the number and dose of administration to provide a toxicological guideline for a better clinical application of CNPs