RESUMO
Neogambogic acid (NGA), which possesses a variety of anticancer activities, is visualized as an anticancer bioactive ingredient. However, the huge vascular stimulation, poor aqueous solubility, and short half-life restricted its clinical use. In this work, an effective nanocarrier was explored to reduce toxicity and enhance the tumor-targeted delivery. Two liposomal formulations, neogambogic acid liposomes (NGA-L), and hyaluronic acid-coated neogambogic acid liposomes (HA-NGA-L) were prepared and characterized with high encapsulation efficiency, slow pattern of drug release, narrow size distribution and higher stability. The cytotoxicity and cellular uptake of HA-NGA-L were higher than those of NGA-L in MDA-MB-231 cells (high CD44 expression), while no obvious differences in MCF-7 cells with (low CD44 expression), suggesting the CD44-mediated cellular internalization of hyaluronic acid-modified liposomes enhanced the cytotoxicity. Mechanistically, elevation of Bax and caspase-3 as well as downregulation of Bcl-2 led to cell apoptosis. Besides, the vascular stimulation and the hemolysis test indicated good safety of HA-NGA-L. In addition, HA-NGA-L was the effective nanocarrier to repress tumor proliferation in MDA-MB-231 tumor xenograft mouse through CD44 mediated active targeting without any obvious histopathological abnormities on major organs. Immunohistochemistry analysis revealed the enhanced elevation of Bax and caspase-3, and reduced expression of Bcl-2 contribute to apoptosis in tumors. Meanwhile, HA-NGA-L increased the AUC and t1/2 by 5.34-fold and 3.94-fold, respectively. In summary, the present study shows that HA-NGA-L may be safe and effective for the tumor-targeted delivery of neogambogic acid.
RESUMO
BACKGROUND: The symptoms of frequent nausea and vomiting, inability to eat, and fluid imbalance caused by hyperemesis gravidarum (HG) seriously impact the quality of life of pregnant women. In some serious cases, it is even necessary to terminate the pregnancy, and threatens the life of the pregnant woman. A great many of studies have proved that HG can be effectively treated by traditional Chinese medicine (TCM) external treatment. Nevertheless, its relative effectiveness and safety haven't yet been confirmed because of the variety of TCM external treatment. Therefore, we will use the method of network meta-analysis to verify the effectiveness and safety of different types of TCM external treatment for the HG. METHODS: In this study, English and Chinese literatures that meet the requirements will be searched in EMBASE, PubMed, Cochrane Library, Web of Science, CnKI, VIP, Wanfang, and CBM. Regardless of whether blinding is used or not, all randomized controlled trials (RCTs) using TCM external treatment for the HG will be included. Then, Stata 16.0 will be used to conduct a series of pairwise meta-analysis. WinBUGS 1.4.3 and Stata 16.0 will be used to conduct Bayesian network meta-analysis to evaluate the relative results of different TCM external treatments for the HG. The quality included in the study will be evaluated through the classification of Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: This study will evaluate the effectiveness and safety of TCM external treatment for the HG according to the primary and secondary outcomes, and we rank different kinds of TCM external treatments in accordance with effectiveness. The primary outcomes are the intensity of nausea and vomiting. Secondary outcomes include quality of life, adverse outcome of pregnant women, adverse outcome of fetal, duration of hospitalization and so on. CONCLUSION: This study will provide more convincing and detailed information of TCM external treatment for the HG, and the reference value for clinical treatment. INPLASY REGISTRATION NUMBER: INPLASY 202090089.
