Galactosylated nanocrystallites of insoluble anticancer drug for liver-targeting therapy: an in vitro evaluation.
OBJECTIVE
Low solubility in water has become an intrinsic property of many anticancer drugs, which poses a hurdle in the translation from the bench to the clinic. In this study, we developed a facile method to prepare 10-hydroxycamptothecin (HCPT) nanocrystallites and testified their feasibility for liver-targeting therapy.


METHODS
HCPT nanocrystallites were prepared under the soft template effect of galactosylated chitosan. The internalization profile, intracellular trafficking, drug activity and cell viability were evaluated by exposing these nanocrystallites to human hepatocellular carcinoma HepG2 cells.


RESULTS
Galactosylated chitosan located on the HCPT nanocrystallites not only stabilized the formulation in aqueous medium, but also enhanced the cellular internalization through an asialoglycoprotein receptor-mediated pathway. These nanocrystallites also exhibited the advantages of nuclear entry and active HCPT delivery, and consequently better anticancer cytotoxicity could be achieved.


CONCLUSIONS
These data strongly support the superior properties of galactosylated HCPT nanocrystallites on liver-targeting therapy.
Wei
Wei
W
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China.
Yue
Zhan-Guo
ZG
Qu
Jian-Bo
JB
Yue
Hua
H
Su
Zhi-Guo
ZG
Ma
Guang-Hui
GH
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D005690:Galactose / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D012995:Solubility
D000970:Antineoplastic Agents; D005690:Galactose