title: On-demand combinational delivery of curcumin and doxorubicin via a pH-labile micellar nanocarrier.
abstract: The combinational delivery of doxorubicin and curcumin in a physically loaded nanocarrier offers the benefits of enhanced therapeutic efficacy and reduced adverse effects, but this strategy often suffers from the slow drug release followed by delayed onset of pharmacological action. This work reported the hydrazone-linked polymer-curcumin conjugate micelles containing physically loaded doxorubicin to address this problem; the ester-linked conjugate micelles were produced as the control. The pH-labile spherical micelles were less than 100 nm with a loading at 9.3 ± 0.5% (w/w, Curcumin) and 2.5 ± 0.1(w/w, Doxorubicin). Both agents were released at a faster rate in the pH-labile micelles compared to the control. The confocal laser scanning microscopy revealed a time-dependent co-localization of both agents in HepG2 cells. The IC50 of pH-labile conjugate micelles without doxorubicin in HepG2 cells was 27.7 ± 5.3 (μM), whereas the co-loaded micelles was lowered to 10.8 ± 3.4 (μM) (Cur-equivalent dose). The combination index calculation demonstrated a synergistic action of both agents in the co-loading nanocarrier. The current work provided an efficient nanocarrier system to achieve rapid on-demand drug release without onset delay of therapeutic action, which might add value to the clinical translation of the combinational delivery systems.
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Fan
authors.affiliation: Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, People's Republic of China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: wangzheng2006@tju.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: zhaoyj@tju.edu.cn.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004357:Drug Synergism; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000737:chemistry; D008823:Micelles; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol; D003474:Curcumin
keywords: Combinational delivery; Curcumin; Doxorubicin; Micelle; Stimuli-responsive