Study On TPGS Modified Liposome As Carrier Of Doxorubicin

TPGS has been utilized for numerous applications in pharmaceutical dosage forms. Its chemical structure contains both a lipophilic and hydrophilic moiety, making it similar to a conventional surface-active agent. The unique chemical properties of this compound have suggested its use as a solubilizer, an emulsifier, an absorption enhancer, and a potential controlled drug release vehicle. TPGS could also inhibit P-glycoprotein and enhance the cytotoxicity of anticancer drugs such as doxorubicin, vinblastine and paclitaxel.In this study, TPGS modified doxorubicin liposome were prepared by (NH4)2SO4-gradiend method. Preparation and physicochemical properties of TPGS modified doxorubicin liposome were closely investigated in comparison with conventional doxorubicin liposome. The drug encapsulation efficiency was determined via cationic exchange resin; drug release in vitro was carried out with dialysis bag; the morphological characterization of liposomes was observed by transmission electron microscopy; particle size distribution and Zeta potential of liposomes were determined by laser nanoparticle size analyzer; stability constant(Ke),drug leakage and the influence of fetal bovine serum on the particle size distribution was also investigated.TPGS-modified doxorubicin liposomes exhibited uniform shape with drug encapsulation efficiency higher than95%; TPGS modified liposomes exhibited significant stability during storage as well as in serum. TPGS reduced drug leakage from liposomes during storage in spite of enhancing the release in vitro.In our study, we studied plasma pharmacokinetics (PK) of TPGS modified doxorubicin liposome in SD rat and compared with free DOX and conventional doxorubicin liposome. Non-compartment analysis was utilized for the PK analysis, and PK parameters were calculated using DAS version2.1.1. The plasma concentration-time profiles were entirely different from those of free DOX. In addition, compared to conventional doxorubicin liposome, AUCO-24h of TPGS modified doxorubicin was larger,but MRTO-24h was shorter. We also study the antitumor efficacy in tumor-bearing ICR mice through determination of tumor growth and tuomor weight inhibition.TPGS modified doxorubicin liposome showed improved antitumor efficacy in comparisom with free DOX and conventional doxorubicin liposome.we studied the cytotoxicity and cellular uptake of these formulations in both MCF-7cells and MCF-7/ADR cells in vitro.we observed that TPGS modified doxorubicin liposome enhanced the intracellular uptake of doxorubicin in MCF-7/ADR cells in comparison with free DOX and the conventional, whereas free DOX showed the highest intracellular accumulation in MCF-7.To be mentioned, the cellular uptake of liposome formulation with sucrose in MCF-7/ADR cells was twice as high as of that of the liposome formulation without sucrose. Furthermore, MTT assay revealed that TPGS could enhance the cytotoxicity both in MCF-7cells and MCF-7/ADR cells, indicating its potential use for reversing drug resistance.Finally, in vivo antitumor effect was evaluated using H22-tumor bearing ICR mice as the animal model. Mice treated with physiological saline used as negative control. Formulations of doxorubicin were administered via tail vein at a dose of5mg/kg at5,7,9and11days after tumor inoculation. Compared to free DOX and conventional liposome, TPGS modified doxorubicin liposome resulted in a greater inhibition of tumor growth but also significantly reduced tumor weight, suggesting that its improved antitumor efficacy of doxorubicin.