Nanocarriers mediated delivery of methotrexate is instrumental in treating auto-immune diseases and cancer
Methotrexate (MTX) is used extensively in cancer chemotherapy and for the management of various autoimmune disorders such as rheumatoid arthritis and psoriasis. The well reported mechanism of action of MTX is to obstruct the dihydrofolatereductase (DHFR) which inhibits the duplication of purines. MTX suppresses the inflammation and modulates the host’s immune system during the pathogenesis of rheumatoid arthritis and psoriasis. However, MTX has unpredictable absorption features and displays various adverse effects. In past couple of decades, nano-bioengineered systems have been expansively harnessed to develop countless nanometric systems to expedite the delivery of biomedical agents to their site of action. These functional nanostructured systems have proven their efficacy while managing various dreadful disorders. This review provides an insight of recent advancements in the development of various MTX loaded nanostructured carriers utilized so far for management of cancer and other autoimmune disorders such as Rheumatoid arthritis and Psoriasis. Efforts also have been made to illustrate the potential of nanotechnology-based systems to deliver MTX effectively to targeted site.
Introduction
The utmost priority of any biomedical researcher is to attain the highest therapeutic effectiveness along with the least adverse effects. Dreadful diseases like cancer demand skilled personnel to provide chemotherapy and radiotherapy to achieve better results. Physicochemical properties and pharmacodynamics of drugs are the main factors which decide the effectiveness of therapy in case of cancer, rheumatoid arthritis and psoriasis. Although treatment options with conventional dosage forms have gained acceptance owing to their cost-effectiveness, simple and patient-friendly approach, attention towards newly emerged nanotechnology-based drug delivery systems, for example, polymeric nanoparticles, solid lipid nanoparticles, liposomes, micelles, hybrid nanoparticles, dendrimers, liquid nanocarriers and others, have fascinated the scientists owing to their target specificity, usefulness and minimum hazardous effects [1].
Methotrexate (MTX), an antimetabolite, is extensively utilized in numerous clinical disorders viz. rheumatoid arthritis, psoriasis, cancer and so on [2]. US-FDA has approved MTX for the treatment of Crohn’s disease [3]. At higher dosages, MTX acts as anticancer agent by inhibiting the activity of the dihydrofolate reductase enzyme which is essential for the biosynthesis of DNA [2]. It was also reported that, at lower dose, MTX and its metabolite work as an anti-inflammatory agent [4,5]. MTX-associated prohibition of dihydrofolate reductase and other folate-linked enzymes triggers the over production of adenosine, an anti-inflammatory chemical, which lead to immunosuppression [6].
Nanostructured delivery systems are perceived as fascinating alternatives for the management of countless ailments through passive and active targeting [7]. Nanotechnology has proven to help in attaining maximum therapeutic efficacy of delivered drugs. The efficacy of treatment is related with the efficacy of drug to reach the site of action and alter the biological functionalities of diseased cells, thereby minimizing damage to the normal cells [7]. Nanocarriers take benefit of their exclusive characteristics such as subtle-size (10–500 nm), low toxicity, ability to release drug in controlled manner, biodegradability, long residence time in systemic circulation, high surface-to-volume ratio and enhanced permeation and retention (EPR) effect [8].
This review revisits the potential uses of MTX in various clinical conditions such as cancer, and other autoimmune ailments like psoriasis and arthritis. We discuss about the role of novel drug delivery systems in improving the scopes of MTX delivery in the treatment of cancers, psoriasis and arthritis.
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Samarth Kumar, Neeraj kumar Garg, Ashay Jain, Ajay Khopade, Prachi Pandey, Krutika K. Sawant, Nanocarriers mediated delivery of methotrexate is instrumental in treating auto-immune diseases and cancer, Journal of Drug Delivery Science and Technology, 2023, 104969, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2023.104969.