Paclitaxel and curcumin co-loaded mixed micelles: Improving in vitro efficacy and reducing toxicity against Abraxane ?

被引:25
作者
Riedel, Jennifer [1 ]
Calienni, Maria Natalia [2 ,3 ,4 ]
Bernabeu, Ezequiel [1 ,9 ]
Calabro, Valeria [5 ,6 ]
Lazaro-Martinez, Juan Manuel [7 ]
Prieto, Maria Jimena [2 ,3 ]
Gonzalez, Lorena [8 ]
Martinez, Carolina Soledad [2 ,3 ]
Alonso, Silvia del Valle [2 ,3 ]
Montanari, Jorge [2 ,3 ,4 ]
Evelson, Pablo [5 ,6 ]
Chiappetta, Diego A. [1 ,9 ]
Moretton, Marcela A. [1 ,9 ]
机构
[1] Univ Buenos Aires, Fac Farm & Bioquim, Catedra Tecnol Farmaceut 1, Buenos Aires, DF, Argentina
[2] Univ Nacl Quilmes, Dept Ciencia & Tecnol, Lab Bionanotecnol, Bernal, Argentina
[3] IMBICE CONICET CCT La Plata, Grp Biol Estruct & Biotecnol GBEyB, Buenos Aires, DF, Argentina
[4] Univ Nacl Hurlingham UNAHUR, Buenos Aires, DF, Argentina
[5] Univ Buenos Aires, Fac Farm & Bioquim, Dept Quim Analit & Fisicoquim, Catedra Quim Gen & Inorgan, Buenos Aires, DF, Argentina
[6] Univ Buenos Aires, Fac Farm & Bioquim, Inst Bioquim & Med Mol IBIMOL, CONICET, Buenos Aires, DF, Argentina
[7] Univ Buenos Aires, Fac Farm & Bioquim, Inst Quim & Metab Farmaco IQUIMEFA, Dept Quim Organ,CONICET, Buenos Aires, DF, Argentina
[8] Univ Buenos Aires, Fac Farm & Bioquim, Dept Quim Biol, Buenos Aires, DF, Argentina
[9] Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina
关键词
Breast and ovarian cancer; Mixed micelles; Curcumin; Paclitaxel; Soluplus; Zebrafish; OVERCOME MULTIDRUG-RESISTANCE; OXIDATIVE STRESS; BREAST-CANCER; LIPID-PEROXIDATION; OVARIAN-CANCER; KAPPA-B; DELIVERY; ANTIOXIDANT; ZEBRAFISH; MODEL;
D O I
10.1016/j.jddst.2021.102343
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Paclitaxel (PTX) is one of the most effective antineoplastic drugs employed for breast and ovarian cancer therapy. However, the neurotoxicity associated with PTX administration represents one of its main drawbacks reducing patient life quality. Recently, curcumin (CUR) has been explored as a neuroprotective agent due to its antioxidant properties. Then, the co-encapsulation of PTX and CUR in a mixed micellar formulation could promote a neuroprotective effect of the micellar system and optimize breast and ovarian cancer therapy. PTX-CUR-loaded Soluplus:TPGS mixed micelles were developed and characterized by nuclear magnetic resonance, scattering techniques and transmission electron microscopy. In vitro cytotoxicity was evaluated in MDA-MB-231 and SKOV3 cancer cells. The in vitro antioxidant performance of CUR-loaded nanoformulations was confirmed employing lipid peroxidation inhibition and DPPH colorimetric assays. The neuroprotective effect of the micellar formulations was evaluated on zebrafish larvae. Mixed micelles demonstrated an excellent colloidal stability, before and after freeze-drying. Nanoformulations with both drugs demonstrated the best in vitro anticancer performance versus the commercially available nanoformulation Abraxane? in breast and ovarian cancer cells lines. The in vitro antioxidant properties of the mixed micelles with CUR were confirmed and their in vivo potential neuroprotective effect was assessed in the zebrafish model.
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页数:12
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