title: A macromolecular prodrug strategy for combinatorial drug delivery.
abstract: A novel macromolecular prodrug strategy was developed for the combinatorial delivery of two poorly water-soluble drugs, dexamethasone and doxorubicin. In this work, dexamethasone was firstly conjugated onto a water-soluble modified polysaccharide by an acid-labile hydrazone linkage. The resultant macromolecular prodrug had an amphiphilic character and could self-assemble into spherical polymeric micelles in aqueous system. With these micelles, doxorubicin was then encapsulated into their hydrophobic cores. For the conjugated dexamethasone and encapsulated doxorubicin, they could exhibit independent and acid-sensitive release characteristics. For the doxorubicin-loaded prodrug micelles, they were easily be internalized by living cells and showed obvious antitumor activity.
authors.affiliation: DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Li
authors.affiliation: DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Medical College, Dongguan 523808, China.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Lin
authors.affiliation: DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Di
authors.initials: D
authors.lastname: Gao
authors.affiliation: DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China. Electronic address: ceszhlm@mail.sysu.edu.cn.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
mesh_terms: D000272:Adipates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000494:pharmacology; D003907:Dexamethasone / Q000737:chemistry* / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004338:Drug Combinations; D004339:Drug Compounding; D006493:Heparin / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D014867:Water
chemical_list: D000272:Adipates; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D008823:Micelles; D011355:Prodrugs; D014867:Water; D003907:Dexamethasone; D004317:Doxorubicin; D006493:Heparin; C010011:adipic dihydrazide
keywords: Acid-sensitive release; Combinatorial drug delivery; Macromolecular prodrug; Polymeric micelles; Self-assembly