Solubility Enhancement of Methotrexate by Solid Nanodispersion Approach for the Improved Treatment of Small Cell Lung Carcinoma

Author(s): Karthikeyan Rajalingam, Venkateshwaran Krishnaswami, Shanmugarathinam Alagarsamy, Ruckmani Kandasamy*

Journal Name: Current Topics in Medicinal Chemistry

Volume 21 , Issue 2 , 2021

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Graphical Abstract:


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.

Keywords: Methotrexate, Carcinoma, Nanodispersion, Solubility, SCLC treatment, Anticancer potential.

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Article Details

Year: 2021
Published on: 04 September, 2020
Page: [140 - 150]
Pages: 11
DOI: 10.2174/1568026620999200904120241
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