The Study Of The Therapic Effect Of Exercise Combining With Paclitaxel-loaded Nanoparticles Drug Delivery Systems In Cancer

Exercise is becoming readily accepted as a beneficial adjunct therapy to maintain or enhance quality of life in cancer patients. Nanoparticles have been widely investigated as drug delivery systems. Both of them can have beneficial effects on the treatment of tumors, but the data is limited, and there is no information on their combined effects. Prevention and treatment of malignant cancer have become an issue of growing concern in both research and clinical practice. With more understanding in pathologic features and biological characteristics of cancer and advances in the state-of-art techniques for early diagnoses and adjuvant therapy, new solutions for cancer focus more on multidisciplinary approach and combined therapy. During recent years, researchers at home and abroad have been investigating the effects of exercise on cancer patients undergoing operative, radio/chemo, and endocrine therapy. Encouraging evidence showed that aerobic exercise can strengthen both physical and psychological functions, fight fatigue, and improve overall quality of life for cancer patients. In this article, experimental evidences and reviews of exercise and cancer were gathered, and on that basis, all the benefits of aerobic exercise on cancer were summarized and possible mechanisms were analyzed. To investigate and prove the benefits and mechanism of exercise on cancer, an animal model with lewis lung cancer cells was set up, and treatment for the animal model included both paclitaxel-loaded nanoparticles and exercise. The experimental results suggested a positive effect of exercise as an adjunctive therapy and partly proved some mechanisms.Methods:Drug encapsulation efficiency (EE) and loading content (LC) of the nanoparticles were evaluated by high-performance liquid chromatography. Nanoparticles diameters and structures were determined by dynamic light scattering and transmission electron microscopy. In vitro release was performed in phosphate-buffered saline (pH 7.4) at 37°C, and in vivo experiments were realized in lung cancer-bearing mice. Nanoparticles localization and accumulation were observed by confocal microscopy in Lewis Lung Cancer cells. Female C57BL/6J mice were transplanted with LLC cells and randomly assigned to one of six groups: normal saline, paclitaxel, exercise, paclitaxel-loaded nanoparticles, paclitaxel combining with exercise or paclitaxel-loaded nanoparticles combining with exercise group. Mice were intraperitoneally administered with paclitaxel or paclitaxel-loaded nanoparticles, then exercise groups performed treadmill running for 12 days. The tumor volumes were measured everyday. At the final day, peritoneal macrophages of mice were harvested and analyzed by flow cytometer. The acetonitrile extracts of blood and tissues were analyzed by high-performance liquid chromatography (HPLC) system.Results: Similar EE and LC values were obtained for nanoparticles from direct dissolution method and those from dialysis. L- and D-PLA/PEG mixed nanoparticles present higher drug encapsulation ability than separate ones due to stereocomplexation. nanoparticles diameters are enlarged by drug-loading. Faster drug release was obtained for nanoparticles from direct dissolution than those by dialysis. Compared with current clinical formulation and nanoparticles from dialysis, paclitaxel-loaded nanoparticles from direct dissolution showed the highest antitumor ability. The data in vivo suggests the nanoparticles drug delivery system improves the bioavailability of paclitaxel in vivo. Exercise impacts the phagocytosis of macrophages. In addition as an adjuvant treatment, exercise increases curative effect of paclitaxel-loaded nanoparticles.Conclusion: The L- and D-PLA/PEG mixed nanoparticles from direct dissolution method present many advantages such as easy formulation and absence of toxic organic solvents, which shows great potential as carrier of hydrophobic drugs. The nanoparticles drug delivery system improves the bioavailability of paclitaxel in vivo. In addition as an adjuvant treatment, exercise increases curative effect of paclitaxel-loaded nanoparticles.