title: 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.affiliation: Department of Chemistry, Duke University, Durham, North Carolina, USA.
authors.forename: Meredith T
authors.initials: MT
authors.lastname: Morgan
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: David J
authors.initials: DJ
authors.lastname: Kroll
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Griset
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carnahan
authors.forename: Michel
authors.initials: M
authors.lastname: Wathier
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
authors.forename: Govindarajan
authors.initials: G
authors.lastname: Manikumar
authors.forename: Mansukh C
authors.initials: MC
authors.lastname: Wani
authors.forename: Mark W
authors.initials: MW
authors.lastname: Grinstaff
mesh_terms: 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
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D002214:Capsules; D050091:Dendrimers; D002166:Camptothecin