负载达沙替尼和橙皮苷的纳米制剂及其抗癌活性的临床前评价

Q3 Pharmacology, Toxicology and Pharmaceutics International Journal of Pharmaceutical Quality Assurance Pub Date : 2023-09-25 DOI:10.25258/ijpqa.14.3.20
Moinuddin ., Sachin Neekhra, SK Swarnkar, Puneet Gupta, Deepa Gupta, Alok Khunteta, Ujjwal Kaushik, Saeem Ahmad
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引用次数: 0

摘要

在这项研究中,我们旨在开发达沙替尼/橙皮苷负载sln用于慢性髓性白血病(CML)。利用高剪切均质机进行合成,采用“中心复合设计(CCD)”来增强负载达沙替尼/橘子皮苷的sln。优化后的SLNs的PDI、粒径和平均包封效率分别为0.12%、162.3 nm和93%。因此,通过增加孔普醇的总量和超声时间,可以提高多分散性。波洛沙姆188的含量对降低SLN的多分散性指数有显著影响,其包封效率(EE)为93%。通过TEM、SEM、FTIR、DSC和HPLC分析,对sln进行了表征,并通过体外和体外细胞活力试验(MTT)对其抗癌效果进行了评价。含有达沙替尼和橙皮苷的sln具有圆形和球形,直径为200nm。DSC和FTIR测试显示了药物与辅料的相容性。对优化后的SLN制剂进行48小时的药物释放观察。研究发现,该药物释放其药物成分的时间较长,其中30%的药物在前4小时释放,其余76%的药物在接下来的48小时释放。根据独立研究测定的IC50值,达沙替尼、橙皮苷和SLN分别为33.97、5158和4.03 μg/mL。SLN与游离药物的比较表明,SLN具有更强的细胞毒性。在这项研究中,制备了达沙替尼和橙皮苷负载的慢性髓性白血病(CML) sln,并使用无毒性辅料的新配方方法对其进行了评估。
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Dasatinib and Hesperidin Loaded Nano Formulation and Preclinical Evaluation for Anticancer Activity
In this study, we aimed to develop Dasatinib/hesperidin-loaded-SLNs for chronic myeloid leukemia (CML). Utilizing a high-shear homogenizer for the synthesis, “central composite design (CCD)” was used to enhance the dasatinib/hesperidin loaded-SLNs. The optimized SLNs had PDI, particle size, and average entrapment efficiency of 0.12%, 162.3 nm, and 93%, respectively. Therefore, by enhancing the total amount of Compritol as well as sonication time the polydispersity was increased. Poloxamer 188 content had a significant influence in decreasing the polydispersity index and the entrapment efficiency (EE) of the SLN was found to be 93%. Through TEM, SEM, FTIR, DSC, and HPLC analysis, SLNs were characterized, and their anticancer efficiency was assessed in both in-vitro and in-vitro cell viability tests (MTT). SLNs containing dasatinib and hesperidin have rounded and spherical shape having a diameter of 200 nm. DSC and FTIR tests showed compatibility between the drugs and excipients. The drug release from optimized SLN formulation was under observation for 48 hours. It was found that the medication released its drug components over a protracted period of time, with 30% of the drug being released in the first four hours and the remainder 76% in the next 48 hours. According to the IC50 values determined by an independent study, dasatinib, hesperidin, and SLN were 33.97, 5158, and 4.03 μg/mL, respectively. A comparison of SLN and free drugs revealed that SLN was more effective at cytotoxicity. In this study, dasatinib and hesperidin-loaded SLNs for chronic myeloid leukemia (CML) against HL60 human leukemia cell lines were prepared and evaluated using a novel formulation approach free of toxic excipients.
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来源期刊
International Journal of Pharmaceutical Quality Assurance
International Journal of Pharmaceutical Quality Assurance Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
CiteScore
0.80
自引率
0.00%
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0
期刊介绍: INTERNATIONAL JOURNAL OF PHARMACEUTICAL QUALITY ASSURANCE is a quarterly international journal publishing the finest peer-reviewed research in the field of Pharmaceutical Quality Assurance and Pharmaceutical Analysis on the basis of its originality, importance, disciplinary interest, timeliness, accessibility, elegance, and surprising conclusions. IJPQA also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.
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