Synergistic effects of multidrug/material combination deliver system for anti-mutidrug-resistant tumor.

Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.

Effect of Walking Exercise and Intestinal Cleansing Interval on Bowel Preparation Quality, a Single-Blind, Randomized Controlled Trial.

BACKGROUND AND AIMS: High-quality intestinal preparation could promote intestinal cleanliness and lead to more accurate diagnosis, which patients will benefit from. This study aimed to explore the effectiveness of walking exercise and intestinal cleansing interval in bowel preparation before colonoscopy. METHODS: A randomized controlled single blind study was conducted during August 2021 to February 2022. Patients requiring colonoscopy were randomly divided into three groups: 0 step, 5000 steps or 10,000 steps during the intestinal preparation. Participants took the same intestinal cleansing drugs 4-6 h prior to the procedure: 2L-dose polyethylene glycol (PEG). RESULTS: A total of 300 patients were enrolled in the experiment (100 patients per group), and the baseline information of the three groups was close. The BBPS of right (0-step group vs 5,000-step group vs 10,000-step group: 1.78 ± 0.65 vs 1.88 ± 0.54 vs 2.36 ± 0.69, p < 0.001), transverse (0-step group vs 5,000-step group vs 10,000-step group: 2.09 ± 0.78 vs 2.18 ± 0.61 vs 2.59 ± 0.71, p < 0.001) and left (0-step group vs 5,000-step group vs 10,000-step group: 2.01 ± 0.91 vs 2.24 ± 0.59 vs 2.51 ± 0.60, p < 0.001) colon in 10,000-step group were significantly higher than others, respectively. And we also drew the same conclusion in the aspect of ADR. The adverse events and patients' satisfaction had no differences between the two groups. Moreover, intestinal cleansing interval (< 5.12 h) was only effective in BBPS of right colon (p < 0.001) and left colon (p = 0.039). CONCLUSIONS: This study suggested that participants took 10,000-step walking exercise and took PEG 5.12 h prior to the procedure were effective in routine pre-procedure cleanout for standard colonoscopy. NAME OF REGISTRY: Effect of starting time of bowel cleansing and walking exercise after bowel cleansing on bowel preparation: A prospective randomized controlled study. REGISTRATION NUMBER: ChiCTR2100049214.