In this paper, orally nanocrystal capsules were produced using nanocrystal formulations in order to optimize dissolution properties of poorly soluble drug glimepiride and improve its bioavailability. The important preparation variables, such as stabilizers, the power input and the time length of ultrasonication on the mean particle size and polydispersity index were investigated systematically, and the optimal values were 0.2% glimepiride (w/v), 1.2% Lipoid S100, 0.6% PEG 6000 (w/v), 0.6% PVPK 30 (w/v), 500 W and 2 min, respectively. Characterization of glimepiride nanocrystal was carried out by X-ray powder diffractometry, differential scanning calorimetry and scanning electron microscopy. In vitro dissolution test, the nanocrystal-loaded capsules of glimepiride showed an evident increase in dissolution rate compared to micronized and market capsules. The in vivo studies demonstrated that a marked enhancement of bioavailability of nanocrystal-loaded capsules was superior compared to the marketed formulation and microcrystal-loaded capsules, which may reduce the risk of side effect by allowing a reduction in either the dose or its frequency of administration.

Hypoxia in tumors can lead to insufficient oxygen supply during sonodynamic therapy (SDT), which in turn strengthens tumor resistance to sonodynamic efficacy. To conquer hypoxia in tumors and improve the treatment effectiveness, we developed oxygen self-production red blood cell (RBC) carrier system to decompose tumor endogenic H2O2 into O2 and combine triplex cancer therapy: ferryl-hemoglobin (ferryl-Hb), sonodynamic, and chemical therapy. Both hydrophilic sonosensitizer and doxorubicin (DOX) were encapsulated inside RBCs (DOX/Mn-TPPS@RBCs). The drug release can be improved by combining the effects of H2O2 and ultrasonic irradiation. Here, we introduced a contrast agent, meso-tetra (4-sulfonatephenyl) porphyrinate manganese­(III) complex (Mn-TPPS), which could be used to enhance the signal intensity of magnetic resonance imaging (MRI) of the tumor site. The feasibility of Mn-TPPS as a sonosensitizer was investigated during SDT. Importantly, DOX/Mn-TPPS@RBCs overcame hypoxia in the tumor and improved the efficacy of SDT owing to the O2 generation by the catalase-catalyzed decomposition of tumor endogenic H2O2. Hemoglobin was simultaneously oxidized into highly oxidative ferryl-Hb species by H2O2 and reactive oxygen species, resulting in cytotoxicity. Overall, this drug delivery system is a promising therapeutic agent involving in situ production of oxygen inside the tumor, triplex therapy, and MRI.

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The purpose of the present study was to evaluate the tissue distribution and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension compared with 2-ME solution both in vitro and in vivo. 2-ME nanosuspension was made by nanoprecipitation-high-frequency ultrasonication method with the particle size of 168.4 ± 3.2 nm and the zeta potential of -29.79 ± 1.89 mV. The overall targeting efficiency (TE(Q)) of 2-ME nanosuspension was improved from 28.71 to 51.95% in the lung of rats. MTT assay showed that 2-ME nanosuspension could significantly enhance the in vitro cytotoxicity against lewis lung carcinoma (LLC) cells compared with the 2-ME solution, the IC(50) at 72 h was reduced from 6.35 µM for 2-ME solution to 3.56 µM for 2-ME nanosuspension. The antitumor activity in vivo was investigated in C57BL/6 mice bearing LLC, and the results indicated that 2-ME nanosuspension not only exhibited significant suppression of the tumor growth when compared with that of positive group or cyclophosphamide group at the same dose, but also enhanced the spleen indices. Overall, 2-ME nanosuspension could mainly deliver the drug to lungs and made the drug accumulate in the lungs, so 2-ME nanosuspension has a possible lung cancer therapeutic potential.

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