Facile Fabrication of Dual-Activatable Gastrointestinal-Based Nanocarriers for Safe Delivery and Controlled Release of Methotrexate.

Colon cancer is emerging as one of the most common cancers worldwide, ranking in the top three in morbidity and mortality. Oral methotrexate (MTX) has been employed as a first-line treatment for various cancers, such as colon, breast, and lung cancer. However, the complexity and particularity of the gastrointestinal microenvironment and the limitations of MTX itself, including severe adverse effects and instability, are the main obstacles to the safe delivery of MTX to colon tumor sites. Herein, an innovative oral administrated anticancer therapeutic MTX@Am7CD/SDS NPs equipped with both pH and temperature sensitivity, which could effectively prevent MTX@Am7CD/SDS NPs from being degraded in the acidic environment mimicking the stomach and small intestine, thus harboring the potential to accumulate at the site of colon lesions and further release intestinal drug under mild conditions. In cellular assays, compared with free MTX, MTX@Am7CD/SDS NPs showed a favorable tumor inhibition effect on three tumor cell lines, as well as excellent cell uptake and apoptosis-inducing effect on SW480 cells. Therefore, this work provides a feasible solution for the safe use of MTX in the treatment of colon cancer and even other intestinal diseases.

Experimental and molecular docking investigation of the inclusion complexes between 20(S)-protopanaxatriol and four modified ß-cyclodextrins.

20(S)-Protopanaxatriol (PPT) is a type of ginsenoside isolated from panax notoginseng or ginseng, which is an essential ingredient in functional food, healthcare products and traditional medicine. However, the research and development of PPT are restricted due to its poor solubility. To circumvent the associated problems, a novel bridged-bis [6-(2,2'-(ethylenedioxy) bis (ethylamine))-6-deoxy-ß-CD] (H4) was successfully synthesized. The four inclusion complexes of the mono-[6-(1,4-butanediamine)-6-deoxy-ß-CD] (H1), mono-[6-(2,2'-(ethylenedioxy) bis (ethylamine)-6-deoxy-ß-CD] (H2) and their corresponding bridged bis(ß-CD)s (H3, H4) with PPT were prepared and studied by UV, 1H NMR, 2D ROESY, FT-IR, XRD and SEM technology. The UV-spectrometric titration showed that H1-4 and PPT formed 1:1 inclusion complexes and the binding constants were 297.61, 322.25, 937.88 and 1742 M-1, respectively. It was further revealed that the size/shape-matching relationship, hydrophobic interactions and hydrogen bond interactions play the crucial role in determining the stability of H1-4/PPT inclusion complexes. The solubility of PPT was evidently enhanced by193, 265, 453 and 593 times after the formation of inclusion complexes with H1-4, respectively. Furthermore, molecular docking was used to verify the inclusion mode of H4/PPT inclusion complex and also to investigate the stability of H4/PPT in water phase. The molecular simulation results agreed well with the experimental results. This research provides an effective way to obtain novel PPT-based functional food and healthcare products.