ABSTRACT
OBJECTIVE:To study in vivo tissue distribution of genistein-loaded MePEG-PLGA copolymer micelle in mice. METHODS:HPLC method was used to determine the concentrations of genistein in plasma and tissues (heart,liver,spleen, lung, kidney) of mice. The determination was performed on Dikma Diamonsil C18 colunm with mobile phase consisted of methanol-water (60:40,V/V) at the flow rate of 1.0 mL/min. The detection wavelength was set at 260 nm,and the column temperature was 35 ℃. The sample size was 10 μL. 48 mice were divided into emulsion group and micelle group,with 24 mice in each group. They were given 40 mg/kg genistein emulsion or genistein-loaded MePEG-PLGA copolymer micelle via tail vein. The contents of genistein in plasma and tissues (heart,liver,spleen,lung,kidney) were detected 5,30,90 min after medication. AUC0-90 min and mean residence time(MRT)were compared. RESULTS:The content of genistein in micelle group was higher than emulsion group 5,30,90 min after medication,and the content of genistein in liver tissue was lower than emulsion group 5,30 min after medication. Compared with emulsion group,AUC0-90 min and MRT of genistein in plasma of mice in micelle group were increased significantly(P<0.01);AUC0-90 min and MRT of genistein in liver tissue were decreased significantly(P<0.05). AUC0-90 min of genistein in renal tissue was increased significantly (P<0.05),without statistical significance of other differences (P>0.05). CONCLUSIONS:genistein-loaded MePEG-PLGA copolymer micelle can increase the distribution of genistein in plasma,reduce the distribution of it in liver tissue so as to improve therapeutic efficacy and reduce drug hepatotoxicity.
ABSTRACT
OBJECTIVE: To prepare heparan sulfate-vitamin E succinate (HDV) amphipathic copolymers and explore the pharmaceutical properties of doxorubicin (DOX)-loaded HDV copolymer micelles (DOX/HDV). METHODS: HDV copolymers were prepared by amide reaction and its structure was confirmed by H-NMR. DOX/HDV micelles were prepared by ultrasonic method. The particle size, morphology, Zeta potential, drug loading, entrapment efficiency, and in vitro drug release and cytotoxicity were evaluated. RESULTS: HDV amphipathic copolymers were synthesized successfully. The particle size, PDI value and Zeta potential of drug-loaded micelles were (105.0±7.3) nm, (0.239±0.484) and (-21.4±2.6) mV, respectively. The encapsulation and drug loading rate were (76.22±0.76)% and (9.53±0.58)%, respectively. The results of drug release test in vitro showed that DOX was released slowly from the micelles. Cytotoxicity experiments indicated that blank micelles had no apparent toxicity against both tumor cells and normal cells. However, DOX/HDV micelles could inhibit the tumor cells growth obviously. CONCLUSION: HDV copolymers can effectively load DOX with properties of drug sustained release and enhanced cytotoxicity against tumor cells in vitro, which indicates that HDV may be a potential candidate for cancer therapy.
ABSTRACT
OBJECTIVE: To enhance the anticancer activity of doxorubicin(DOX) by conjugating DOX and vitamin E succinate (VES) and loading the conjugate into hyaluronic acid-octadecylamine (HA-C18) copolymer micelles. METHODS: DOX and VES were conjugated by amide reaction. DOX-VES/HA-C18micelles were prepared via a probe-type ultrasonication technique. The morphology of the micelles was determined using a transmission electron microscopy (TEM).Dynamic light scattering (DLS) technique was used to determine the particle size distribution, hydrodynamic diameters, and stability of the micelles. Ultracentrifugation was exploited for measuring the drug loading (DL) and encapsulation efficiency (EE), and the in vitro release was investigated using a dialysis tubing. The cellular uptake and cellular distribution of drug-loaded micelles in MCF-7 cells were observed by fluorescence microscope, and the fluorescence intensity of DOX was evaluated by flow cytometer. The cytotoxicity of free DOX and drug-loaded micelles was tested by MTT assay against MCF-7 cells. RESULTS: DOX-VES/HA-C18 showed a nearly spherical morphology and good stability in PBS (pH 7.4) and 10% FBS. The particle size and zeta potential were (184.6±9.42) nm and (-20.7±1.23) mV, respectively. The DL and EE were (15.8±2.85)% and (94.2±1.32)%, respectively. DOX-VES/HA-C18had a good controlled drug release property. Furthermore, DOX-VES/HA-C18with accumulation in nucleipresented higher anti-tumor activity than free DOX and DOX/HA-C18. CONCLUSION: DOX-VES conjugate has synergistic anti-tumor effect and good application prospects.
ABSTRACT
OBJECTIVE: To synthesize hyaluronic acid-octadecene (HOY) copolymers by terminal thiolation modification of hyaluronic acid (HA), prepare doxorubicin-loaded micelles and investigate its pharmaceutical characteristics. METHODS: HOY copolymers were synthesized through Michael addition reaction. The doxorubicin-loaded copolymer micelles were prepared with ultrasonic method, then the particle size, Zeta potential, encapsulation efficiency, drug loading efficiency and in vitro release behavior were studied. RESULTS: HOY copolymers were synthesized successfully. The particle size and Zeta potential of the drug-loaded micelles were (237.2±2.7) nm and (-22.37±0.38) mV, and the encapsulation efficiency and drug loading rate were (89.8±0.011)% and (5.4±0.007)%, respectively. Moreover, the accumulative release of doxorubicin in vitro was about 70% in 48 h, indicating that the drug was released slowly from the micelles. CONCLUSION: This study develops a new micellar system based on terminal modified HA, and provides a reference for the study of HA nanocarrier.