Methotrexate: a detailed review on drug delivery and clinical aspects

Khan, Zulfequar Ahamad; Tripathi, Rahul; Mishra, Brahmeshwar

doi:10.1517/17425247.2012.642362

Cited by 204 publications

(141 citation statements)

References 117 publications

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“…Being able to enter a cell via pinocytosis, a carrier also would allow overcoming the resistance of tumor cells caused by impaired transmembrane transport. Indeed, in the last decade, a burst of research has been conducted on MTX-bearing drug delivery systems, 3,4 including…”

Section: Introductionmentioning

confidence: 99%

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Алексеева¹,

Моисеева²,

Onishchenko³

et al. 2017

IJN

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In a previous study, a formulation of methotrexate (MTX) incorporated in the lipid bilayer of 100-nm liposomes in the form of diglyceride ester (MTX-DG, lipophilic prodrug) was developed. In this study, first, the interactions of MTX-DG liposomes with various human and mouse tumor cell lines were studied using fluorescence techniques. The liposomes composed of egg phosphatidylcholine (PC)/yeast phosphatidylinositol/MTX-DG, 8:1:1 by mol, were labeled with fluorescent analogs of PC and MTX-DG. Carcinoma cells accumulated 5 times more MTX-DG liposomes than the empty liposomes. Studies on inhibitors of liposome uptake and processing by cells demonstrated that the formulation used multiple mechanisms to deliver the prodrug inside the cell. According to the data from the present study, undamaged liposomes fuse with the cell membrane only 1.5–2 hours after binding to the cell surface, and then, the components of liposomal bilayer enter the cell separately. The study on the time course of plasma concentration in mice showed that the area under the curve of MTX generated upon intravenous injection of MTX-DG liposomes exceeded that of intact MTX 2.5-fold. These data suggested the advantage of using liposomal formulation to treat systemic manifestation of hematological malignancies. Indeed, the administration of MTX-DG liposomes to recipient mice bearing T-cell leukemic lymphoma using a dose-sparing regimen resulted in lower toxicity and retarded lymphoma growth rate as compared with MTX.

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Section: Introductionmentioning

confidence: 99%

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Алексеева¹,

Моисеева²,

Onishchenko³

et al. 2017

IJN

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“…[10][11][12] However, long-term use and high-dose Mtx given by systematic administration have been associated with drug resistance and adverse side effects. 13,14 Therefore, it is desirable to develop a system that can deliver Mtx selectively to target tissues and to release the encapsulated Mtx within a short time. 15 In order to deliver encapsulated drug to target tissues efficiently, efforts have been devoted to the development of intelligent delivery systems that respond to specific stimuli, such as pH level, temperature, and redox potential.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis

Zhao¹,

Zhao²,

Yu³

et al. 2017

IJN

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive cartilage and bone destruction. Activated macrophages that overexpress folic acid (FA) receptors play an important role in RA, due to their abundance in inflamed synovial membrane and joints. In an effort to deliver drugs to the inflamed tissues, multifunctional FA receptor-targeting and pH-responsive nanocarriers were developed. They were composed of lipids, polyethylene glycol (PEG)–poly(lactic- co -glycolic acid) (PLGA) forming a hydrophilic shell, FA around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core. PCADK also acts as a pH-responsive material. Methotrexate (Mtx) was encapsulated in the nanoparticles, which exhibited pH-responsive release in vitro. Cellular uptake and cytotoxicity experiments revealed that FA-PEG-PLGA/PCADK–lipid nanoparticles loaded with Mtx (FA-PPLNPs) exhibited superior cellular uptake and higher cytotoxicity to activated macrophages than PPLNPs/Mtx. The therapeutic effect of FA-PPLNPs/Mtx in RA was confirmed in an adjuvant-induced arthritis rat model. These results suggest that the multifunctional folate receptor-targeting and pH-responsive nanocarriers are promising for the treatment of RA.

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“…Methotrexate is a drug used widely for the treatment of different types of cancers and autoimmune diseases like rheumatoid arthritis [22]. Tripathi et al, [23] have reported that it has been used as a first line drug in many autoimmune diseases pemphigus, myasthenia gravis, uveitis, chronic active hepatitis.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Antioxidant Action of Murraya Koenigii and Plumeria Rubra Extracts Enhance Hepatoprotective Efficacy Against Methotrexate Induced Liver Injury

Pal

Desai

Highland

2017

Int J Pharm Pharm Sci

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Objective: The present study was focussed on evaluating the hepatoprotective capacity of a combination of leaf extracts of Murraya koenigii and Plumeria rubra on drug-induced toxicity in mice liver.Methods: Hydromethanolic and aqueous extracts were prepared from the leaves of Murraya koenigii and Plumeria rubra. A combination of these extracts was tested as a dual formulation (DF). The extracts were evaluated for their antioxidant activity and phytochemical content. Healthy adult male mice were treated in five groups, for 30 d: Control (Group I-Untreated), Group II (Methotrexate at 10 mg/kg Body weight, intraperitoneally), Group III (Methotrexate+Silymarin), Group IV (Methotrexate+hydromethanolic extract of DF-250 mg/kg b.w., orally), Group V (Methotrexate+aqueous extract of the DF-250 mg/kg b.w. orally). After treatment, the animals were necropsied. Blood was collected for serum parameters such as alanine transaminase (ALT), Aspartate transaminase (AST) and γ glutamyl transpeptidase (GGT). Further liver function tests like Alkaline phosphatase (ALP), Phosphorylase as well as Oxidative stress parameters like Lipid peroxidation (LPO), Superoxide dismutase (SOD), Catalase (CAT), along with the liver protein and cholesterol content were analyzed.Results: Administration of both the DF extracts significantly ameliorated the methotrexate-induced toxic effects on all the aforementioned biochemical parameters. The hydromethanolic extract showed significant recovery in the liver function tests like ALT (p<0.05) and AST (p<0.001). Antioxidant stress enzymes like SOD (p<0.001) and Catalase (p<0.001) also showed significant recovery after administration of both the extracts. The other parameters assayed also followed the same trend. Although both the extracts showed remarkable hepatoprotection, the hydromethanolic extract was found to be significantly more potent than the aqueous extract. ConclusionKeywords: Mice, Liver, Dual formulation, Hepatoprotection : The present study concludes that the Dual formulation of the extracts of Murraya koenigii and Plumeria rubra could be an effective hepatoprotective agent due to the synergistic action of the phytoconstituents of both the plants.

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Methotrexate: a detailed review on drug delivery and clinical aspects

Cited by 204 publications

References 117 publications

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis

Synergistic Antioxidant Action of Murraya Koenigii and Plumeria Rubra Extracts Enhance Hepatoprotective Efficacy Against Methotrexate Induced Liver Injury

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