Mechanisms Of Realgar Nanoparticles And Its Formulas In Cancer Therapy

Traditional Chinese medicine(TCM) coming from the great Chinese culture, which had made important contribution to generation and health of the Chinese people,is a characteristic of traditional Chinese culture.With the enhancement of Chinese power,Traditional Chinese medicine also has great development;but compared with western medicine,it still grows slowly to meet the people's need. Because of its complex ingredients,unclear mechanisms of bioactivities and no evidence-based medicine(EBM),TCM will be blocked in developing and research, not to mention coming into international medicine market.Realgar,in which tetraarsenic tetrasulfides(As₄S₄) is the major active ingredient, has been used as an active ingredient of formulations or as a stand-alone drug to treat various diseases in China and Europe for thousands of years.Its promising anticancer activity has attracted increasing attention in the recent years,especially in the treatment of refractory or relapsed acute promyelocytic leukemia(APL) and chronic myelogenous leukemia(CML).A recent development is nanosized realgar,which exhibited improved physical and chemical properties.Deng et al.examined four different suspensions of realgar particles with diameters ranging from 100 to 500 nm for their toxicities towards human umbilical vein endothelial cells,and came to a conclusion that particles of realgar smaller than 150 nm were less toxic to normal cells.Furthermore,compared with conventional-made realgar,realgar nanoparticles exhibited a superior pharmacokinetic profile,such as better maximal concentration (Cmax),serum half-life and bioavailability.Toxicity and anticancer effect both need to be considered in evaluating a drug. Realgar is primarily administered orally or intravenously.Intravenous delivery is inconvenient and may lead to systemic toxicity,while oral administration suffers from low bioavailability and complications derived from the first-pass metabolism in the liver.Poor water solubility adds further burden for the delivery of realgar.Previous studies have shown that realgar is toxic in long-term use and can cause severe liver damage.Given the scenario that realgar would likely to be administered on a daily basis to cancer patients,an alternative way of delivering realgar is highly desirable to increase the drug's effectiveness while minimizing its toxic effects.Transdermal drug delivery(TDD) is a drug absorption system via skin to come to the effective blood drug concentration through blood capillary to make the drugs work on the organ or diseased region.Compared with conventional syringing or orally application,TDD has more advantages,such as providing a steady plasma drug concentration;reducing or changing the typical dosing schedule easily;and avoiding the first-pass metabolism effect for drugs with poor oral bioavailability.Angiogenesis,namely many new blood vessels formation,is a key step to support solid tumors growth compared with the complicated statuses of the growth of the solid tumors.Antiangiogenic therapy would provide an alternative target to identify new anticancer drugs,which would give an indirect strategy compared to a direct strategy that targeted on the tumor cell itself.If combined these two strategies, we would get a more powerful method to handle tumor cells in vivo.Vascular endothelial growth factor(VEGF),one of the stimulatory angiogenic factors,was chosen to visualize one stage of angiogenesis in this study because it selectively affected a number of endothelial cell functions acquired during angiogenesis.Here,we firstly utilized TDD system to deliver realgar nanoparticles and its formulas.The aims of this study were to investigate whether this system could deliver realgar nanoparticles and its formulas efficiently with low toxicity and to elucidate the mechanisms of realgar nanoparticles and its formulas in vivo.This study represented a much easier option for realgar its formulas in the further clinical application to patients.