Preparation and evaluation of redox sensitive mixed micelles containing paclitaxel
10.16438/j.0513-4870.2020-0390
- VernacularTitle:载有紫杉醇的氧化还原敏感混合胶束的制备及评价
- Author:
Dong-ying LÜ
1
;
Shuo HUANG
1
;
Lu-ping SHA
1
;
Yong-xue GUO
1
Author Information
1. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
- Publication Type:Research Article
- Keywords:
paclitaxel;
italic>D-α-tocopherol polyethyleneglycol 1 000 succinate;
redox sensitivity;
isulfide bond;
nano-micelle
- From:
Acta Pharmaceutica Sinica
2020;55(6):1320-1326
- CountryChina
- Language:Chinese
-
Abstract:
The structural modification of nano-micellar polymer carriers can not only increase the solubilization of insoluble drugs, but also make drug-loaded carriers aggregate in tumor tissues. In this paper, paclitaxel (PTX) was used as a model drug, D-α-tocopherol polyethyleneglycol 1 000 succinate (TPGS) modified by disulfide bond (-S-S-) and oleic acid (OA) was synthesized and mixed micelles were prepared with different molar ratios of sodium deoxycholate (NADC), and TPGS and NADC mixed micelles modified by thioether bond were synthesized for comparative study. The effects of the critical micelle concentration (CMC) of the modified polymer and the molar ratio of TPGS-OA and NADC on the physical and chemical properties of the micelle were investigated. Finally, the redox drug release ability of disulfide bond and thioether bond was compared. The results showed that when the molar ratio of TPGS-OA to NADC decreased, the drug loading increased, but the stability decreased. When the molar ratio was 3∶1, the particle size, potential and entrapment efficiency of TPGS-S-S-OA/NADC were 96.24 ± 0.14 nm, -24.4 mV and (98.7 ± 0.08)%, respectively, hemolysis rate of mixed micelles is less than 2%. The disulfide modified mixed micelles released PTX completely within 5 h in 10 mmol·L-1 H2O2 environment (pH 7.4), which was similar to that of thioether modified micelles. It was also found that the stability of micelles decreased when the pH value was low. All animal experiments were in accordance with ethical standards and were approved by the Animal Experimental Center of Shenyang Pharmaceutical University (No.211002300032403). In this study, we mainly developed stable nano-micelle carriers which can target drug release in tumor heterogeneous environment.
