The CNT-PDMS composite has been widely adopted in flexible devices due to its high elasticity, piezoresistivity, and biocompatibility. In a wide range of applications, CNT-PDMS composite sensors were used for resistive strain measurement. Accordingly, the percolation threshold 2%~4% of the CNT weight ratio in the CNT-PDMS composite was commonly selected, which is expected to achieve the optimized piezoresistive sensitivity. However, the linear range around the percolation threshold weight ratio (2%~4%) limits its application in a stable output of large strain (>20%). Therefore, comprehensive understanding of the electromechanical, mechanical, and electrical properties for the CNT-PDMS composite with different CNT weight ratios was expected. In this paper, a systematic study was conducted on the piezoresistivity, Young’s modulus, conductivity, impedance, and the cross-section morphology of different CNT weight ratios (1 to 10 wt%) of the CNT-PDMS composite material. It was experimentally observed that the piezo-resistive sensitivity of CNT-PDMS negatively correlated with the increase in the CNT weight ratio. However, the electrical conductivity, Young’s modulus, tensile strength, and the linear range of piezoresistive response of the CNT-PDMS composite positively correlated with the increase in CNT weight ratio. Furthermore, the mechanism of these phenomena was analyzed through the cross-section morphology of the CNT-PDMS composite material by using SEM imaging. From this analysis, a guideline was proposed for large strain (40%) measurement applications (e.g., motion monitoring of the human body of the finger, arm, foot, etc.), the CNT weight ratio 8 wt% was suggested to achieve the best piezoresistive sensitivity in the linear range.
Background Halofuginone hydrobromide (HF) is a synthetic analogue of the naturally occurring quinazolinone alkaloid febrifugine, which has potential therapeutic effects against breast cancer, however, its poor water solubility greatly limits its pharmaceutical application. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of vitamin E, which can self-assemble to form polymeric micelles (PMs) for encapsulating insoluble anti-tumor drugs, thereby effectively enhancing their anti-cancer effects. Methods HF-loaded TPGS PMs (HTPMs) were manufactured using a thin-film hydration technique, followed by a series of characterizations, including the hydrodynamic diameter (HD), zeta potential (ZP), stability, drug loading (DL), encapsulation efficiency (EE), and in vitro drug release. The anti-cancer effects and potential mechanism of HTPMs were investigated in the breast cell lines MDA-MB-231 and MCF-7, and normal breast epithelial cell line Eph-ev. The breast cancer-bearing BALB/c nude mouse model was successfully established by subcutaneous injection of MDA-MB-231 cells and used to evaluate the in vivo therapeutic effect and safety of the HTPMs. Results The optimized HTPMs had an HD of 17.8±0.5 nm and ZP of 14.40±0.1 mV. These PMs exhibited DL of 12.94 ± 0.46% and EE of 90.6 ± 0.85%, along with excellent storage stability, dilution tolerance and sustained drug release in pH-dependent manner within 24 h compared to free HF. Additionally, the HTPMs had stronger inhibitory effects than free HF and paclitaxel against MDA-MB-231 triple-negative breast cancer cells, and little toxicity in normal breast epithelial Eph-ev cells. The HTPMs induced cell cycle arrest and apoptosis of MDA-MB-231 by disrupting the mitochondrial membrane potential and enhancing reactive oxygen species formation. Evaluation of in vivo anti-tumor efficacy demonstrated that HTPMs exerted a stronger tumor inhibition rate (68.17%) than free HF, and exhibited excellent biocompatibility. Conclusion The findings from this study indicate that HTPMs holds great clinical potential for treating triple-negative breast cancer.
Background Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models. Methods Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice. Results Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice. Conclusion Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.
HF-loaded TPGS polymer micelles (HTPM) were developed to improve the anticoccidial effect of loaded drugs by enhancing cellular take up, denaturing merozoites inside infected cells, and restoring the gut microbiome.
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