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OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL）， investigate its physicochemical properties， magnetic effect and photothermal effect， so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS： Using DOX as model drug， TiO2@Fe3O4 as photosensitizers and magnetic materials， DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed； particle size and Zeta potential were detected； encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution， in vitro release behavior of the liposome was investigated by dialysis method， and the release curves at different temperatures （at 37， 43 ℃） were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species （ROS） in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS： Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion， and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm； polydispersity index was 0.107； Zeta potential was （－7.76±3.41）mV； encapsulation efficiency was （92.3±3.2）％. Under the external magnetic field， the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution， the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃， the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser （808 nm） irradiation time， the temperature of the liposome kept rising， which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS： DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully， which has uniform appearance， good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency， and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.
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Objective To prepare and characterize a thermo-sensitive liposomes co-loaded with IR-780 and doxorubicin (D0X). Methods Membrane hydration method and ammonium sulfate gradient method were used to prepare IR-780/D0X thermo-sensitive liposomes (DITSL). The particle size, zeta potential and polydispersity coefficient (PDI) of liposomes were measured by Malvern laser particle size analyzer, and the drug release characteristic of DITSL induced by laser was also detected. Results DITSL loading both IR-780 and D0X was successfully prepared. The encapsulation efficiency of IR-780 and D0X was (94.47 ± 8.57) % and (92.52 ± 7.61)%, respectively; the average particle size was (138.98 ± 8.74) nm, with slight negative potential; the PDI was 0.32 ± 0.02. The drug release rate of DITSL was about 80.1% after laser radiation (0. 8 W/cm2, 5 min) and the highest temperature of DITSL was 54.2°C. Conclusion The prepared DITSL has high drug encapsulation efficiency, appropriate particle size, high photo-thermal conversion efficiency, good temperature sensitivity and laser-induced thermal drug release property, which lays a foundation study for the combination treatment of tumors with photo-thermal therapy and chemotherapy.
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Objective To investigate the tumor inhibition effect of paclitaxel long-circulating thermo sensitive liposomes (PLTL) in mice bearing Lewis lung carcinoma cells. Methods A tumor-bearing mouse model was established, and the mice were randomly divided into five groups: control, heating, paclitaxel (PTX), paclitaxel thermo sensitive liposomes (PTL), and PLTL groups. The living status was observed in the mice. The volume and weight of the tumor were measured. The morphological changes in the tumor cells were observed f by HE staining and apoptosis of the tumor cells was determined by flow cytometry. Results The inhibition rate of tumor in PTX, PTL and PLTL groups was 48.87%, 57.22%and 78.87%, respectively. The apoptotic rate of tumor cell in PTX, PTL and PLTL groups was (42.7 ± 3 .8)%, (54.6 ± 2.9)%and (69.7 ± 5.0)%, respectively. Conclusions PLTL, as compared with PTX and PTL, has an evident thermo sensitive feature and increases the anticancer effect of paclitaxel remarkably in combination with local hyperthermia.
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Objective To prepare long-circulating temperature-sensitive liposomes with paclitaxel( LTSLP ),develop methods for determination of paclitaxel,related substances and monostearoyl phosphatidylcholine( MSPC ) in LTSLP,and the haemolysis of LTSLP in vitro. Methods HPLC-UV methods for paclitaxel content and related substances and HPLC-CAD method for MSPC in LTSLP were established and validated. Spectrophotometric method was used to determine hemolysis in vitro. Results There was a good linear relationship between peak area and concentration within the range of 60. 39-181. 17μg·mL-1 . Recovery and precision of the method for determination of paclitaxel content met the requirements. Specificity,sensitivity,and system suitability for related substances were consistent with requirements. There was a good linear relationship between peak area and concentration within the range of 1. 5-50. 0μg·mL-1 for the determination of MSPC with good specificity,sensitivity and recovery. Paclitaxel contents in three batches of self-prepared LTSLP were between 90. 0% and 110. 0%,single related substances were below 0. 5% and total impurities were below 2. 0%. There was almost no hemolysis in vitro. Conclusion The methods for determining paclitaxel content,related substances and haemolysis can be used to assess the quality of LTSLP. Self-produced LTSLP consistently meet the quality standards.