Protective effects of psoralen polymer lipid nanoparticles on doxorubicin - induced myocardial toxicity

Abstract Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.

Nanotargeted agents: an emerging therapeutic strategy for breast cancer.

Breast cancer is the most common female cancer worldwide and represents 12% of all cancer cases. Improvements in survival rates are largely attributed to improved screening and diagnosis. Conventional chemotherapy remains an important treatment option but it is beset with poor cell selectivity, serious side effects and resistance. Nanoparticle drug delivery systems bring promising opportunities to breast cancer treatment. They may improve chemotherapy by targeting drugs to tumors, generating high drug concentrations at tumors providing slow release of the drug, increased drug stability and concomitant reductions in side effects. The nanotechnology-based drug delivery approaches and the current research and application status of nano-targeted agents for breast cancer are discussed in this review to provide a basis for further study on targeted drug delivery systems.

A review of pharmacological and clinical studies on the application of Shenling Baizhu San in treatment of Ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: The prescription of Shenling Baizhu San (SLBZS) was derived from the Song Dynasty "Taiping Huimin Heji Ju Fang", which was a representative prescription for treating spleen asthenic diarrhea. The prescription comprised of 10 herbs for treating weak spleen and stomach. It describes symptoms like eating less, loose stools, cough, shortness of breath and tired limbs. SLBZS has been reported to be capable of eliminating discomfort when it is administered for treating irritable bowel syndrome and diarrhea. This traditional Chinese medicine (TCM) formula has been widely used for improving gastrointestinal dysfunction and modifying the immune response to inflammation. AIM OF THE STUDY: This review is aimed to provide the up-to-date information on the pharmacology and clinical research of SLBZS in the treatment of ulcerative colitis (UC), and to discuss the research findings and possible deficiencies, hoping to better guide the clinical application and scientific research of SLBZS in the treatment of UC. MATERIALS AND METHODS: Relevant studies from 2004 to 2018 on SLBZS in the treatment of UC mechanism and curative effect were collected from ancient books, pharmacopoeia, reports, thesis via library and Digital databases (PubMed, CNKI, Google Scholar, Web of Science, SciFinder, Springer, Elsevier, etc). RESULTS: SLBZS could regulate inflammatory factors and intestinal flora, and ERK/p38 MAPK signaling pathway may be one of its targets. In addition, clinical research results show that SLBZS has a good therapeutic effect on UC, and the adverse reactions are small. CONCLUSION: Although SLBZS has achieved some success in the treatment of UC, there are still some scientific gaps. There is a lack of uniform standards for constructing UC animal models, and some methods of modeling through environmental and dietary interventions are not reproducible, and there is a lack of uniform dosing regimen standards. SLBZS doses follow the tradition and lack toxicological validation. Therefore, more specific toxicological research models are essential. The clinical application of SLBZS requires reassessment and standardization. Although all clinical research reports randomly assigned patients to different groups, most did not describe a detailed method of randomization and no description of the analysis data. In addition, extensive in vitro studies and further in-depth molecular studies are essential for the determination of mechanisms that have been performed in all in vivo experiments on animal models and patients.

Polymer-lipid hybrid nanoparticles: A novel drug delivery system for enhancing the activity of Psoralen against breast cancer.

A polymer-lipid hybrid nanocarrier was developed to encapsulate psoralen (PSO) to improve its water solubility and bioavailability. The effects of PSO-loaded polymer-lipid hybrid nanoparticles (PSO-PLNs) on breast cancer MCF-7 cells were investigated. PSO-PLNs were prepared through a nanoprecipitation method and were optimized by a central composite design-response surface methodology using particle size and entrapment efficiency as indices. Dynamic light scattering and transmission electron microscopy analysis confirmed the physicochemical characterizations of PSO-PLNs, which had an average size of 93.44 ±â€¯2.39 nm and a zeta potential of -27.63 ±â€¯0.31 mV. In vitro drug release of PSO-PLNs was evaluated using dialysis and showed a delayed release compared with free PSO. The in vivo anticancer efficiency of PSO-PLNs was appreciated using a MCF-7 breast tumor model. Administration of PSO-PLNs showed similar antitumor efficacy but lower toxicity compared with doxorubicin. Our designed nanocarriers successfully optimized the pharmacokinetics of PSO via improved systemic delivery.