title: Effect of molecular weight of PGG-paclitaxel conjugates on in vitro and in vivo efficacy.
abstract: Polymeric prodrugs are one of the most promising chemotherapeutic agent delivery approaches, displaying unique drug release profiles, serum stability, formulation flexibility, and reduced drug resistance. One of the most important aspects of a polymeric prodrug, albeit a less-extensively studied one, is the polymer's molecular weight, which affects particle formation, drug release and PK/PD profiles, drug stability, and cell uptake; these factors in turn affect the prodrug's maximum tolerated dose and anticancer efficacy. Poly(L-γ-glutamylglutamine) (PGG) is a linear polymer designed to improve the therapeutic index of attached drugs. In this study we selected poly(L-γ-glutamylglutamine)-paclitaxel (PGG–PTX), as a model system for the methodical investigation into the effects of the poly(L-γ-glutamylglutamine) backbone molecular weight on its pharmacological performance. The polymeric prodrug was characterized by NMR, DLS and GPC-MALS, and its anticancer activity in vitro and in vivo was assessed. Herein we present data which provide valuable insight into improving anticancer polymer-based prodrug design and development.
authors.affiliation: Institute for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China.
authors.forename: Danbo
authors.initials: D
authors.lastname: Yang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ying
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Bai
authors.forename: Wendy D
authors.initials: WD
authors.lastname: Taylor
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Clamme
authors.forename: Erick
authors.initials: E
authors.lastname: Co
authors.forename: Padmanabh
authors.initials: P
authors.lastname: Chivukula
authors.forename: Kwok Yin
authors.initials: KY
authors.lastname: Tsang
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011506:Proteins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D011506:Proteins; C548171:poly(gamma-glutamylglutamine)paclitaxel; D017239:Paclitaxel