title: Well-defined diblock brush polymer-drug conjugates for sustained delivery of paclitaxel.
abstract: Using the 3(rd) generation Grubbs' catalyst as the initiator, diblock brush polymer drug conjugates (BPDCs) were synthesized by sequential ring-opening metathesis polymerization (ROMP) of a hydrophilic poly(ethylene glycol) (PEG)-based norbornene (NB)-functionalized macromonomer and a hydrophobic paclitaxel (PTXL)-based NB-functionalized monomer. These amphiphilic diblock BPDCs had well-defined structures, with narrow molecular weight distributions (Mw/Mn = 1.10-1.16). They self-assembled into multi-molecular nanostructures in aqueous solutions. Although the PTXL moieties were connected to the backbone with cycloacetal-based conjugation linkages, the cleavage of these linkages from the assemblies of diblock BPDCs was relatively slow and exhibited limited acid-sensitivity, indicating a significant influence of the macromolecular structure and assembly of BPDCs on their drug release behaviour. The cytotoxicity study not only showed that the diblock BPDCs are therapeutically effective against cancer cells, but also revealed a correlation between cytotoxicity and grafting structures of BPDCs. In summary, the results obtained in this work provide new insight into the structure-dependent properties of brush polymer-based drug delivery systems.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA. ccheng8@buffalo.edu.
authors.forename: Jiong
authors.initials: J
authors.lastname: Zou
authors.forename: Yun
authors.initials: Y
authors.lastname: Yu
authors.forename: Yukun
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Chen
authors.forename: Wing-Cheung
authors.initials: WC
authors.lastname: Law
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
authors.forename: Chong
authors.initials: C
authors.lastname: Cheng
mesh_terms: D002208:Caproates / Q000737:chemistry; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007783:Lactones / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry*; D015394:Molecular Structure; D009636:Norbornanes / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry
chemical_list: D002208:Caproates; D004337:Drug Carriers; D007783:Lactones; D046911:Macromolecular Substances; D009636:Norbornanes; D011108:Polymers; D013778:Tetrazolium Salts; D013844:Thiazoles; C070380:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; C046060:2-norbornene; D011092:Polyethylene Glycols; C121056:caprolactone; D017239:Paclitaxel