title: Dendrimer versus linear conjugate: Influence of polymeric architecture on the delivery and anticancer effect of paclitaxel.
abstract: The relative difference in polymeric architectures of dendrimer and linear bis(poly(ethylene glycol)) (PEG) polymer in conjugation with paclitaxel has been described. Paclitaxel, a poorly soluble anticancer drug, was covalently conjugated with PAMAM G4 hydroxyl-terminated dendrimer and bis(PEG) polymer for the potential enhancement of drug solubility and cytotoxicity. Both conjugates were characterized by 1NMR, HPLC, and MALDI/TOF. In addition, molecular conformations of dendrimer, bis(PEG), paclitaxel, and its polymeric conjugates were studied by molecular modeling. Hydrolysis of the ester bond in the conjugate was analyzed by HPLC using esterase hydrolyzing enzyme. In vitro cytotoxicity of dendrimer, bis(PEG), paclitaxel, and polymeric conjugates containing paclitaxel was evaluated using A2780 human ovarian carcinoma cells. Cytotoxicity increased by 10-fold with PAMAM dendrimer-succinic acid-paclitaxel conjugate when compared with free nonconjugated drug. Data obtained indicate that the nanosized dendritic polymer conjugates can be used with good success as anticancer drug carriers.
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Jayant J
authors.initials: JJ
authors.lastname: Khandare
authors.forename: Sreeja
authors.initials: S
authors.lastname: Jayant
authors.forename: Ajay
authors.initials: A
authors.lastname: Singh
authors.forename: Pooja
authors.initials: P
authors.lastname: Chandna
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Nicholi
authors.initials: N
authors.lastname: Vorsa
authors.forename: Tamara
authors.initials: T
authors.lastname: Minko
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D017239:Paclitaxel / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel