In this work, we report on an ATP-responsive low-molecular-weight polyethylenimine (LMW-PEI)-based supramolecular assembly. It formed via host–guest interaction between PEI (MW = 1.8 kDa)-α-cyclodextrin (α-CD) conjugates and PEI1.8k-phenylboronic acid (PBA) conjugates. The host–guest interaction between PEI1.8k-α-CD and PEI1.8k-PBA was confirmed by the 2D-NOESY chromatogram experiment and competition test. The ATP-responsive property of the supramolecular assembly was evaluated by a series of ATP-triggered degradation and siRNA release studies in terms of fluorescence resonance energy transfer, agarose gel electrophoresis assay, and the time course monitoring of the particle size and morphology. Confocal laser scanning microscopy confirmed the intracellular disassembly of the supramolecular polymer and the release of siRNA. The supramolecular assembly showed high buffering capability and was capable of protecting siRNA from RNase degradation. It had high cytocompatibility according to in vitro cytotoxicity and hemolysis assays. LMW-PEI-based supramolecular assembly facilitated cellular entry of siRNA via energy-dependent endocytosis. Moreover, the assembly/SR-A siRNA polyplexes at N/P ratio of 30 was most effective in knocking down SR-A mRNA and inhibiting uptake of modified LDL. Taken together, this work shows that ATP-responsive LMW-PEI-based supramolecular assembly is a promising gene vector and has potential application in treating atherosclerosis.

Reconstituted high density lipoprotein (rHDL) is a biomimetic nanoparticle with plaque targeting and anti-atherosclerotic efficacy. In this work, we report on a strategy to rational design of lovastatin (LOV)-loaded spherical rHDL (LOV-s-rHDL) for efficient and safe anti-atherosclerotic therapy. Briefly, three LOV-s-rHDLs were formulated with LOV/s-rHDL at ratios of 8:1, 10:1, and 15:1 upon their respective median-effect values (D m). The combined inhibitory effect between LOV and s-rHDL of different LOV-s-rHDL formulations on DiI-labeled oxLDL internalization was systemically investigated in RAW 264.7 cells based on the median-effect principle. Median-effect analysis demonstrated that the optimized LOV-s-rHDL was formulated with a ratio of 10:1 (D m LOV:D m s‑rHDL), in which LOV and s-rHDL carrier showed the best synergistic effect, presumably ascribed to their inhibitory effect on CD36 and SR-A expression according to the Western blot analysis. In vivo pharmacodynamics studies showed that the optimized LOV-s-rHDL displayed the most pronounced anti-atherosclerotic effect on decreasing plaque area and reducing the MMP level following an 8-week dosing regimen. In vivo atherosclerotic plaque targeting analysis revealed that s-rHDL had potent plaque targeting efficacy, probably owing to the interaction between apoA-I and scavenger receptor B-I. Furthermore, we observed that the optimized LOV-s-rHDL exhibited a favorable safety profile as evidenced by the results of a hemolysis assay, cell cytotoxicity study, and in vivo safety test. Collectively, the rational design of the biomimetic LOV-s-rHDL based on the median-effect analysis provides an efficient strategy to achieve a synergistic and safe anti-atherosclerotic therapy.

Objective: Chinese rhubarb is a promising Chinese medicine for the promotion of gastrointestinal function. This study was conducted to investigate the safety and efficacy of Chinese rhubarb administered via ultrasound delivery in promoting the early recovery of gastrointestinal function after gastrectomy. Methods: In this prospective randomized controlled study, 100 patients who were scheduled to undergo total or subtotal gastrectomy in Changzhi People's Hospital or Subei People's Hospital from August 2017 to January 2018 were recruited. These patients were randomly assigned into two equal groups before surgery: 50 in the experimental (Chinese rhubarb) group, and 50 in the control (routine nursing) group. After surgery, time to flatus, bowel movement, clear liquid diet, and removal of nasogastric tube were recorded and analyzed. In addition, postoperative pain, postoperative bowel movement-related complications, and postoperative hospital stay duration were also recorded and analyzed. The study was approved by The protocol was approved by the Institutional Review Board of Changzhi People's Hospital and Subei People's Hospital on July 1, 2017 and registered with the Chinese Clinical Trial Registry on December 17, 2018 (registration number: ChiCTR1800020143). Results: Time to flatus (control group 85.68 ± 22.00 hours vs experimental group 73.06 ± 23.42 hours; P = 0.007), bowel movement (5.52 ± 1.56 vs 4.40 ± 1.21 days; P < 0.001), clear liquid diet (6.72 ± 1.16 vs 6.22 ± 1.28 days; P = 0.044), and removal of nasogastric tube (6.30 ± 1.52 vs 5.65 ± 1.58 days; P = 0.044) were significantly shorter in the experimental group compared with the control group, as was the postoperative hospital stay duration (14.30 ± 3.46 vs 12.86 ± 1.36 days; P = 0.006). In addition, better pain relief (P = 0.003) and a lower incidence of postoperative bowel movement-related complications (6 vs 21; P = 0.001) were noted in the experimental group. Conclusion: Ultrasound delivery of Chinese rhubarb is useful to promote the early recovery of gastrointestinal function after gastrectomy.

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