Luliconazole is the first and only anti-fungal agent approved for the short-term treatment of superficial fungal infections. However, commercially available conventional topical dermal drug delivery cargo of luliconazole is associated with certain limitations like lower skin permeation and shorter skin retention of drug. Therefore, present review is an attempt to decode the penetration hurdles in luliconazole topical dermal drug delivery. Moreover, we also summarized the activity of functional nanomaterials based drug delivery systems employed by the scientific fraternity to improve luliconazole efficacy in superficial fungal infections on case-to-case basis. In addition, efforts have also been made to unbox the critically acclaimed mechanism of action of luliconazole against fungal cells. Under the framework of future prospects, we have analyzed the combination of luliconazole with isoquercetin using in-silico docking technique for offering synergistic antifungal activity. Isoquercetin exhibited a good affinity for superoxide dismutase (SOD), a fungal target owing to the formation of hydrogen bond with Glu132, Glu133, and Arg143, in addition to few hydrophobic interactions. On the other hand, luliconazole inhibited lanosterol-14α-demethylase and consequently blocked ergosterol. In addition, nanotechnology and artificial neural network (ANN) derived integrated drug delivery systems may also be explored for augmenting the luliconazole therapeutic efficacy in topical fungal infections. Synergy of ANN models along with topical nanoscaled drug delivery may help to achieve critical quality attributes (CQA) to gain commercial success.
Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with old age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodelling and inflammaging. To counteract the inflammation, synovium pours various inflammatory and immune mediators along with metabolic intermediates which further worsen the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs (Non-steroidal anti-inflammatory drugs), Opioids, SNRIs (Serotonin-norepinephrine reuptake inhibitors), etc addressing symptomatic treatment and functional improvement in lieu of suppressing OA progression. Long term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional herbalism and are promising alternatives with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases are elusive and/or uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggests that, presence of carbonyl group at 2nd, chloro at 6th along with electron withdrawing group at the 7th position exhibited enhanced COX-2 (Cyclo-oxygenase-2) inhibition activity in OA. On the other hand, the presence of a double bond at C2-C3 position of C ring in flavonoids plays an important role in Nrf2 activation. Moreover, with the advancements in the understanding of OA progression, SARs (Structure activity relationships) of phytochemicals and integration with nanotechnology have given great opportunities to develop phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical based drug therapy.
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