Dendrimer-encapsulated camptothecins: increased solubility, cellular uptake, and cellular retention affords enhanced anticancer activity in vitro.
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.
Morgan
Meredith T
MT
Department of Chemistry, Duke University, Durham, North Carolina, USA.
Nakanishi
Yuka
Y
Kroll
David J
DJ
Griset
Aaron P
AP
Carnahan
Michael A
MA
Wathier
Michel
M
Oberlies
Nicholas H
NH
Manikumar
Govindarajan
G
Wani
Mansukh C
MC
Grinstaff
Mark W
MW
D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use; D001672:Biocompatible Materials; D001692:Biological Transport; D001932:Brain Neoplasms; D001943:Breast Neoplasms; D002166:Camptothecin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002214:Capsules; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms; D050091:Dendrimers / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma; D006801:Humans; D008175:Lung Neoplasms; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D002214:Capsules; D050091:Dendrimers; D002166:Camptothecin