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Solubility Enhancement of Methotrexate by Solid Nanodispersion Approach for the Improved Treatment of Small cell Lung Carcinoma.
Current Topics in Medicinal Chemistry ( IF 2.9 ) Pub Date : 2020-12-31 , DOI: 10.2174/1568026620999200904120241
Karthikeyan Rajalingam 1 , Venkateshwaran Krishnaswami 1 , Shanmugarathinam Alagarsamy 1 , Ruckmani Kandasamy 1
Affiliation  

Aims: The present work aimed to develop MT loaded solid Nano dispersion by improving its solubility, half-life and bioavailability in biological system thereby this formulation may be afforded economically.

Background: Small cell lung carcinoma is a type of malignant tumor characterized by uncontrolled cell growth at lung tissues. The potent anti-cancer drug methotrexate (MT) chosen for the present work is poorly soluble in water (BCS type IV class) with short half-life and hepatotoxic effect.

Objective: With the concept of polymeric surfactant to improve the solubility along with wettability of drugs, the present work has been hypothesized to improve its solubility using polyvinyl pyrollidone (PVP K30) polymer and α- tocopheryl polyethylene glycol 1000 succinate (TPGS) surfactant, thereby the bioavailability is expected to get enhanced. By varying the PVP K30 and TPGS ratios different formulations were developed using emulsification process.

Methods: The developed MT loaded solid nanodispersion was further characterized for its particle size, charge, morphology, encapsulation efficiency and in-vitro release behavior etc.

Results: The results of FT-IR spectrometric analysis indicated the compatibility nature of MTX, PVPK30 and TPGS. The developed formulations showed spherical morphology, particle size ranging from 59.28±24.2 nm to 169.33±10.85 nm with a surface charge ranging from -10.33 ± 2.81mV to -9.57 ± 1.2 mV. The in vitro release studies as performed by dialysis bag method showed a sustained release pattern as checked by UV Spectrophotometer. Residual solvent analysis for MTXNDs performed by HPLC indicates there is no residual DMSO in the formulation. Transmission electron microscopic image of MTXNDs revealed that the particles are spherical shaped with a solid core structure. Haemolytic assay indicates that the developed formulation is safe for intravenous administration. Cell culture studies in A549 cells indicates the enhanced cytotoxic effect for the developed formulation.

Conclusion: This proof of study indicates that the developed formulation may have anticancer potential for SCLC treatment.



中文翻译:

通过固体纳米分散方法提高甲氨蝶呤的溶解度以改善小细胞肺癌的治疗。

目的:目前的工作旨在通过提高其在生物系统中的溶解度、半衰期和生物利用度来开发负载 MT 的固体纳米分散体,从而可以经济地提供这种配方。

背景:小细胞肺癌是一种以肺组织细胞生长不受控制为特征的恶性肿瘤。为当前工作选择的强效抗癌药物甲氨蝶呤 (MT) 难溶于水 (BCS IV 类),半衰期短,具有肝毒性作用。

目的:基于聚合物表面活性剂的概念,以提高药物的溶解度和润湿性,目前的工作假设使用聚乙烯吡咯烷酮 (PVP K30) 聚合物和 α-生育酚聚乙二醇 1000 琥珀酸酯 (TPGS) 表面活性剂来提高其溶解度,从而生物利用度有望提高。通过改变 PVP K30 和 TPGS 的比例,使用乳化工艺开发了不同的配方。

方法:对开发的载有 MT 的固体纳米分散体的粒度、电荷、形态、包封效率和体外释放行为等进行了进一步表征。

结果:FT-IR光谱分析结果表明MTX、PVPK30和TPGS的相容性。开发的制剂显示球形形态,粒径范围为 59.28±24.2 nm 至 169.33±10.85 nm,表面电荷范围为 -10.33 ± 2.81mV 至 -9.57 ± 1.2 mV。用透析袋法进行的体外释放研究显示出通过紫外分光光度计检查的持续释放模式。通过 HPLC 对 MTXND 进行的残留溶剂分析表明配方中没有残留的 DMSO。MTXNDs 的透射电子显微图像显示颗粒呈球形,具有实心核结构。溶血试验表明所开发的制剂对于静脉内给药是安全的。

结论:该研究证明表明,所开发的制剂可能具有用于 SCLC 治疗的抗癌潜力。

更新日期:2021-01-11
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