Methotrexate (MTX), typically used as its sodium salt (MTX Na), is a first-line treatments for moderate to severe psoriasis, showing good efficacy. However, its systemic administration is associated with many side effects. Intradermal delivery into psoriatic tissue could offer an alternative approach. However, successful intradermal administration of MTX Na is currently precluded by its physicochemical properties. Moreover, due to its hydrophilic nature, MTX Na is swiftly cleared from the target tissue, necessitating frequent dosing which may affect patient compliance. To address these limitations, we investigated the combination of nanocrystal (NC) and dissolving microneedle (MN) technologies as an alternative approach for localised and sustained intradermal delivery of MTX Na. Poorly water-soluble MTX nanocrystals (MTX NC) were produced by a bottom-up technique with a mean particle size of 678 ± 15 nm. Sustained in vitro drug release was observed over 72 h. The MTX NC were then incorporated into the shafts of dissolving MN arrays with a drug loading of 2.48 mg/array. The MTX NC-loaded MN arrays exhibited satisfactory mechanical strength and insertion capabilities in the skin-simulant Parafilm M® and their shafts dissolved entirely in less than 20 min after insertion into excised neonatal porcine skin. Importantly, in vivo studies in Sprague Dawley rats revealed that the MN arrays were able to deposit approximately 25.1% of the loaded MTX NC in the skin, which acted, in turn, as a drug depot and released the MTX in a sustained manner over 72 h, while minimising MTX systemic exposure. Indeed, 24 h from MN application, 312.70 ± 161.95 µg/g of MTX was retained in the skin at the application site. This was approximately 322-fold higher than the amount of MTX (0.942 ± 0.59 µg/g) retained in the skin after oral administration of MTX Na. Interestingly, even after 72 h after MN application, around 12.5% of the MTX NC deposited in the skin by the MN was retained. In contrast, the maximal blood concentration of MTX achieved following MN application, was only 40% of that measured after oral administration of MTX Na. Accordingly, MTX NC-loaded dissolving MN arrays could be a promising approach for effective localised and sustained intradermal delivery of MTX as a potential enhanced treatment for psoriasis.

Cancer is a major global health concern. Therefore, new treatment options are needed. The phytochemicals have different chemical structures. It also exhibits several other biological activities. Therefore, these compounds are promising anticancer agents. This review aims to identify and assess new candidates for anticancer therapy. Researchers have identified these compounds among the well‐studied plant chemicals and their actions. Thus, these compounds can be used in anticancer therapies. The popularity of phytochemicals has grown. Currently, these are the subjects of extensive investigational studies. However, obstacles remain in its development and translation for clinical use. This is especially true for low bioavailability. These compounds also exhibit a wide range of activities, toxicities, and regulatory activities. These are necessary for the isolation and characterization of phytochemicals. This review discusses these challenges and the recent progress. Emphasis has been placed on integrating traditional knowledge of medicines with current biomedical advancements to augment the efficacy of phytoconstituents for cancer treatment. The review indicates new treatment frameworks with the synergy of traditional systems of medicine (e.g., Traditional Chinese Medicine [TCM] and Ayurveda) and new approaches today, such as nanotechnology and artificial intelligence‐assisted drug discovery. This review also highlights the clinical efficacy of such phytoconstituents and addresses key developmental bottlenecks, such as bioavailability, regulatory barriers, and standardized methods of extraction. These include the extraction methods, delivery systems, and clinical findings. It focuses on the merging of modern and traditional medicine. The goal of this study was to maximize the potential of these phytochemicals. This will help to create successful cancer treatments. A thorough analysis was done using primary databases, namely PubMed, Scopus, Web of Science, and Google Scholar, for articles between 2020 and 2023. The relevant literature was searched using keywords such as phytochemicals, anticancer mechanisms, bioavailability, delivery systems, and clinical efficacy. The selected articles included peer‐reviewed studies that compared the anticancer mechanisms of phytochemicals, challenges encountered in their development, new advances in extraction and delivery technologies, and clinical reports of their therapeutic efficacy. This approach allowed a wide synthesis of existing knowledge around phytochemicals as anticancer drugs. This review summarizes our knowledge of phytochemicals as potential anticancer agents. This finding fills a gap in the literature. This offers new insights into their roles in personalized cancer treatment. This explains the mechanisms of action and challenges in development. This places these compounds at the forefront of, and complements, cancer treatment. Considerable research is required to boost personalized oncology research. This leads to improved patient outcomes.