MAGNETIC RESONANCE IN CHEMISTRY
·
2017
·Vol. 56
·期 1
·37-45
·
IF 1.601
Chen Yu,Qian Zhang,Peng-yao Xu,Yin Bai,Wen-bin Shen,Bin Di,Meng-xiang Su
Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated 1 H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards.
研究领域:
药物分析
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Tao Liu,Tingting Jia,Xia Yuan,Cheng Liu,Jian Sun,Zhenhua Ni,Jian Xu,Xuhui Wang,Yi Yuan
Background Development of polymeric prodrugs of small molecular anticancer drugs has become one of the most promising strategies to overcome the intrinsic shortcomings of small molecular anticancer drugs and improve their anticancer performance.Materials and methods In the current work, we fabricated a novel octreotide (Oct)-modified esterase-sensitive tumor-targeting polymeric prodrug of bufalin (BUF) and explored its anticancer performance against somatostatin receptor 2 overexpressing breast cancer.Results The obtained tumor-targeting polymeric prodrug of BUF, P(oligo[ethylene glycol] monomethyl ether methacrylate [OEGMA]-co-BUF-co-Oct), showed a nanosize dimension and controlled drug release features in the presence of esterase. It was demonstrated by in vitro experiment that P(OEGMA-co-BUF-co-Oct) showed enhanced cytotoxicity, cellular uptake, and apoptosis in comparison with those of free BUF. In vivo experiment further revealed the improved accumulation of drugs in tumor tissues and enhanced anticancer performance of P(OEGMA-co-BUF-co-Oct).Conclusion Taken together, this study indicated that polymeric prodrug of BUF holds promising potential toward the treatment of somatostatin receptor 2 overexpressing breast cancer.
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Wan-Feng Xu,Yun Wang,Hai Huang,Jia-Wei Wu,Yuan Che,Chu-Jie Ding,Quan Zhang,Wei-Ling Cao,Li-Juan Cao
Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori -induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin , Il-6 and Il1b expression through induction of Muc5ac and Occludin , significantly improving hyperacidity and gastric bleeding . As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2 , decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis.
研究领域:
胃肠病学
·
药理学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2015
·
IF 2.59
Meirong Huo,Qinnv Zhu,Qu Wu,Tingjie Yin,Lei Wang,Lifang Yin,Jianping Zhou
ABSTRACT In this study, a novel PTX prodrug , octreotide(Phe)–polyethene glycol–paclitaxel [OCT(Phe)–PEG–PTX], was successfully synthesized and used for targeted cancer therapy. A nontargeting conjugate, mPEG–PTX, was also synthesized and used as a control. Chemical structures of OCT(Phe)–PEG–PTX and mPEG–PTX were confirmed using 1 H nuclear magnetic resonance and circular dichroism. The drug contents in both the conjugates were 12.0% and 14.0%, respectively. Compared with the parent drug (PTX), OCT(Phe)–PEG–PTX, and mPEG–PTX prodrugs showed a 20,000- and 30,000-fold increase in water solubility, respectively. PTX release from mPEG–PTX and OCT(Phe)–PEG–PTX exhibited a pH–dependent profile. Moreover, compared with mPEG–PTX, OCT(Phe)–PEG–PTX exhibited significantly stronger cytotoxicity against NCI–H446 cells (SSTR overexpression) but comparable cytotoxicity against WI–38 cells (no SSTR expression). Results of confocal laser scanning microscopy revealed that the targeting prodrug labeled with fluorescence probe was selectively taken into tumor cells via SSTR–mediated endocytosis. In vivo investigation of prodrugs in nude mice bearing NCI–H446 cancer xenografts confirmed thatOCT(Phe)–PEG–PTX prodrug exhibited stronger antitumor efficacy and lower systemic toxicity than mPEG–PTX and commercial Taxol. These results suggested that OCT(Phe)–PEG–PTX is a promising anticancer drug delivery system for targeted cancer therapy.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Hui-Yun Zhang,Wen-Qian Xu,Yuan-yuan Zheng,Emmanuel Omari-Siaw,Yuan Zhu,Xia Cao,Shan-Shan Tong,Jiang-nan Yu,Xi-ming Xu
Cardiac glycosides could increase intracellular Ca 2+ ion by inhibiting the Na + /K + ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae . The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H 22 tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H 22 cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）