Preparation of thermoresponsive micelles loaded with indocyanine green and doxorubicin for combined therapy in MCF-7 cells / 药学学报

In this study, the thermoresponsive micelles were synthesized with random copolymerization method and the photosensitizer indocyanine green (ICG) was loaded on micelles through the physical adsorption. The light energy was converted into heat energy to increase the temperature after irradiation with near-infrared light. When the phase transition temperature was reached, the micelle was disassembled and the targeted therapy was achieved. The nanoparticles were characterized with a transmission electron microscopy, Fourier transform infrared spectrometer, nuclear magnetic resonance spectrometer and other characterization were used to investigate. The critical micelle concentration (CMC), upper critical solution temperature, the photothermal properties of the carrier and the release of drug triggered by light were investigated after the doxorubicin (DOX) loaded. The carrier was evaluated for toxicity, cellular uptake, the effect of photothermal, the combination of photothermal and chemotherapy; the p(AAm-co-AN)-g-PEG (PAAP) was spherical in shape with a particle size of about 45 nm and a phase transition temperature was about 43℃. The critical micelle concentration was 24 μg·mL-1. The particle size increased to 88 nm after loaded with ICG and DOX which the photothermal effect was obvious. The cumulative release of the drug under the irradiation of near-infrared light (808 nm, 2 W·cm-2, 2 min·h-1) was increased to 59.4% (pH 5.0) after 5 h. The results of the cell experiment indicated that ICG-PAAP was almost non-toxic and uptaken by the lysosomal pathway. The cell killing effect was stronger with combination of chemotherapy (DOX as 20 μg·mL-1) with more than 70% of the cells killed. The results showed that the prepared micelle with low toxicity was thermoresponsive and could be used in combined therapy of tumor under the irradiation of near-infrared light.

Application of magnetic iron oxide nanoparticles in magnetic resonance/photothermal dual-modal imaging / 药学学报

In this study, water-dispersible magnetic iron oxide (Fe3O4) nanoparticles were synthesized with solvothermal method. The nanoparticles were characterized with a transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The in vitro magnetic resonance response and photothermal conversion characteristics of the nanoparticles were evaluated. In addition, the cellular uptake, cytotoxicity and biodistribution were studied. Finally, magnetic resonance/photothermal dual-modal imaging effect of the as-synthesized Fe3O4 nanoparticles was investigated in the tumor-bearing mice. The results showed that the obtained magnetic nanoparticles were uniform with a mean diameter of about 125 nm. Moreover, the superparamagnetic Fe3O4 nanoparticles showed remarkable magnetic resonance response and photothermal conversion properties. The results of cellular experiments showed that the cell viability was nearly 85% even the concentration of the nanoparticles was up to 1 000 μg·mL-1, an indicator of good biocompatibility. In addition, the nanoparticles could be taken up by the tumor cells and then located in the cytoplasm. After intravenous injection, the nanoparticles were tended to enrich in the tumor over time, which is helpful in achieving dual-modal magnetic resonance/photothermal imaging. In sum, the obtained Fe3O4 nanoparticles showed great potential to be applied for multi-modal bio-imaging which may play an important role in the diagnosis of tumors.

Absorption enhancing effects and safety of PAMAM dendrimers on liquiritin / 中国中药杂志

PAMAM dendrimer is one of the most widely studied dendrimers in recent years, which has a large number of functional groups on the surface and cavities inside, specific three-dimensional structure and good biocompatibility, permeability and stability. It has been widely applied in drug and gene carrier fields and may become a new absorption enhancer. In order to study the absorption enhancing effects of PAMAM dendrimers, liquiritin was selected as the model drug, with the protection of spleen and liver, detoxification and other functions, but it had not been widely used in clinical application because of its difficult absorption, first pass effect, and low bioavailability. This topic was based on the two main determinants (solubility and permeability) of intestinal absorption in the body, researched the physicochemical properties of liquiritin, analyzed the transport volume of liquiritin with or without PAMAM dendrimers by using Caco-2 cell model, and analyzed the cytotoxicity of PAMAM dendrimers on Caco-2 cells by MTT experiments. These results showed that 0.1% of the G4 generation PAG can promote the absorption of liquiritin safely and effectively, and it was suitable for further development into a new type of pharmaceutical excipients.

Preparation and in vitro evaluation of doxorubicin-loaded magnetic iron oxide nanoparticles / 药学学报

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.

Preparation and evaluation of enteric-coated and taste masking clarithromycin granules / 药学学报

The study is to prepare taste masking and enteric-coated clarithromycin granules by melting and fluid bed coating technology. Clarithromycin and matrix materials were melted at a certain temperature, and then made into particles by fluidized bed coating. X-ray powder diffraction and scanning electron microscopy were used to identify the crystal and morphology of drug loading granules. In vitro dissolution method was used for the observation of the drug release behavior. The results showed that the drug particles size range was 0.2 - 0.6 mm; the crystal form of clarithromycin in the granule did not change; enteric-coated granules accumulated release in 0.1 mol L(-1) hydrochloric acid in 2 h was less than 10%, while in pH 6.8 phosphate buffer in 1 h was more than 80%. The taste masking and enteric-coated clarithromycin granules not only have good taste masking effect, but also have a good release behavior. It is expected to have better clinical application.