Dendrimer-encapsulated camptothecins: increased solubility, cellular uptake, and cellular retention affords enhanced anticancer activity in vitro.

Abstract

A biocompatible polyester dendrimer composed of the natural metabolites, glycerol and succinic acid, is described for the encapsulation of the antitumor camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The cytotoxicity of the dendrimer-drug complex toward four different human cancer cell lines [human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), non-small cell lung carcinoma (NCI-H460), and glioblastoma (SF-268)] is also reported, and low nmol/L IC(50) values are measured. Cellular uptake and efflux measurements in MCF-7 cells show an increase of 16-fold for cellular uptake and an increase in drug retention within the cell when using the dendrimer vehicle.

• Authors: Meredith T Morgan, Yuka Nakanishi, David J Kroll, Aaron P Griset, Michael A Carnahan, Michel Wathier, Nicholas H Oberlies, Govindarajan Manikumar, Mansukh C Wani, Mark W Grinstaff
• Journal: Cancer research (Cancer Res) Vol. 66 Issue 24 Pg. 11913-21 (Dec 15 2006) ISSN: 0008-5472 [Print] United States
• PMID: 17178889 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Biocompatible Materials
• Capsules
• Dendrimers
• Camptothecin

Topics

• Antineoplastic Agents, Phytogenic (pharmacokinetics, therapeutic use)
• Biocompatible Materials
• Biological Transport
• Brain Neoplasms
• Breast Neoplasms
• Camptothecin (pharmacokinetics, therapeutic use)
• Capsules
• Carcinoma, Non-Small-Cell Lung
• Cell Line, Tumor
• Colorectal Neoplasms
• Dendrimers (pharmacokinetics, therapeutic use)
• Female
• Glioblastoma
• Humans
• Lung Neoplasms
• Magnetic Resonance Spectroscopy
• Solubility