title: Simply mixing with poly(ethylene glycol) enhances the fraction of the active chemical form of antitumor drugs of camptothecin family.
abstract: This paper reveals a new function of poly(ethylene glycol) (PEG) - a common polymer in pharmaceutics - enhancement of the active chemical form of the antitumor drugs of camptothecin (CPT) analogs. All of members in the CPT family confront the severe problem of hydrolysis of the active lactone ring to the inactive carboxylate, leading to not only less efficiency but also more toxicity. Herein, we report that the equilibrium fraction of the active lactone form could be enhanced significantly by simply mixing the drug solution with PEG. For instance, while the equilibrium lactone fraction of topotecan (TPT) was only a bit more than 10% under neutral pH at 37°C, it was increased to nearly 50% in the presence of 40wt.% PEG. Two CPT family members, TPT and 10-hydrocamptothecin, and six PEG agents with molecular weight from 200 to 5000, were tested, and the phenomenon was confirmed to be universal. The underlying reason was further discussed. The in vivo drug efficacy was also observed in a solid tumor model in mice.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Ci
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Guangtao
authors.initials: G
authors.lastname: Chang
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.forename: Jiandong
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D002166:Camptothecin