OBJECTIVE To prepare paclitaxel loaded D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)-modified carboxymethyl chitosan-rhein polymeric micelles (PTX/TPGS-CR PMs) and preliminarily evaluate their performance. METHODS PTX/TPGS-CR PMs was prepared by dialysis method, and the preparation procedure of PTX/TPGS-CR PMs was optimized by single factor with the drug loading, encapsulation rate and particle size as the indicators, then the optimized preparation procedure was verified. The safety of PTX/TPGS-CR PMs was initially investigated by the hemolysis test and the vascular irritation test. The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was studied by MTT assay. Cell uptake experiments were performed by laser confocal microscopy and flow cytometry to investigate the uptake of PTX/TPGS-CR PMs by Hela cells. RESULTS The particle size and PDI of PTX/TPGS-CR PMs prepared by the optimized preparation were (197.3±4.4) nm and (0.131±0.021), respectively. The Zeta potential was (-31.8±0.5) mV. The drug loading and encapsulation efficiency were (48.20±3.03)% and (87.26±4.91)%, respectively. The hemolytic test results showed that the hemolysis rate was less than 1.71%. No obvious irritation was observed after intravenous injection. The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was concentration-and time-dependent. Cell uptake experiments showed that PTX/TPGS-CR PMs could be efficiently uptake by Hela cells. CONCLUSION The PTX/TPGS-CR PMs has high drug loading and encapsulation efficiency, good safety. And they exhibite slightly better antitumor activity in vitro than Taxol®.
BISWAS S, KUMARI P, LAKHANI P M, et al. Recent advances in polymeric micelles for anti-cancer drug delivery[J]. Eur J Pharm Sci, 2016, 83:184-202.
UPADHYAYA L, SINGH J, AGARWAL V, et al. The implications of recent advances in carboxymethyl chitosan based targeted drug delivery and tissue engineering applications[J]. J Controlled Release, 2014, 186:54-87.
DU Q, BIAN X L, XU X L, et al. Role of mitochondrial permeability transition in human hepatocellular carcinoma Hep-G2 cell death induced by rhein[J]. Fitoterapia, 2013, 91:68-73.
WANG X, GUO Y, QIU L, et al. Preparation and evaluation of carboxymethyl chitosan-rhein polymeric micelles with synergistic antitumor effect for oral delivery of paclitaxel[J]. Carbohyd Polym, 2019, 206:121-131.
LIU T, LIU X, XIONG H, et al. Mechanisms of TPGS and its derivatives inhibiting P-glycoprotein efflux pump and application for reversing multidrug resistance in hepatocellular carcinoma[J]. Polym Chem, 2018, 9(14):1827-1839.
SHIEH M, HSU C, HUANG L, et al. Reversal of doxorubicin-resistance by multifunctional nanoparticles in MCF-7/ADR cells[J]. J Controlled Release, 2011, 152(3):418-425.
GUO Y, LUO J, TAN S, et al. The applications of vitamin E TPGS in drug delivery[J]. Eur J Pharm Sci, 2013, 49(2):175-186.
GUO Y, CHU M, TAN S, et al. Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance[J]. Mol Pharm, 2014, 11(1):59-70.
QIU L, WANG X, CAO C, et al. Preparation and characterization of TPGS modifined carboxymethyl chitosanrhein polymeric micelles[J]. J Shenyang Pharm Univ(沈阳药科大学学报), 2019, 36(4):300-307.
XIE Y, SHI B, XIA F, et al. Epithelia transmembrane transport of orally administered ultrafine drug particles evidenced by environment sensitive fluorophores in cellular and animal studies[J]. J Controlled Release, 2018, 270:65-75.
HU X, ZHANG J, YU Z, et al. Environment-responsive aza-BODIPY dyes quenching in water as potential probes to visualize the in vivo fate of lipid-based nanocarriers[J]. Nanomedicine-Uk, 2015, 11(8):1939-1948.
MA Y, HE H, XIA F, et al. In vivo fate of lipid-silybin conjugate nanoparticles: implications on enhanced oral bioavailability[J]. Nanomed-Nanotechnol, 2017, 13(8):2643-2654.
MAEDA H, BHARATE G Y, DARUWALLA J. Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect[J]. Eur J Pharm Biopharm, 2009, 71(3):409-419.
BERNABEU E, CAGEL M, LAGOMARSINO E, et al. Paclitaxel: what has been done and the challenges remain ahead[J]. Int J Pharm, 2017, 526(1-2):474-495.