The world is facing lockdown for the first time in decades due to the novel coronavirus COVID-19 (SARS-CoV-2) pandemic. This has led to massive global economic disruption, placed additional strain on local and global public health resources and, above all, threatened human health. We conducted a review of peer-reviewed and unpublished data, written in English, reporting on the current COVID-19 pandemic. This data includes previously used strategies against infectious disease, recent clinical trials and FDA-approved diagnostic and treatment strategies. The literature was obtained through a systematic search using PubMed, Web of Sciences, and FDA, NIH and WHO websites. Of the 98 references included in the review, the majority focused on pathogen and host targeting, symptomatic treatment and convalescent plasma utilization. Other sources investigated vaccinations in the pipeline for the possible prevention of COVID-19 infection. The results demonstrate various conventional as well as potentially advanced in vitro diagnostic approaches (IVD) for the diagnosis of COVID-19. Mixed results have been observed so far when utilising these approaches for the treatment of COVID-19 infection. Some treatments have been found highly effective in specific regions of the world while others have not altered the disease process. The responsiveness of currently available options is not conclusive. The novelty of this disease, the rapidity of its global outbreak and the unavailability of vaccines have contributed to the global public's fear. It is concluded that the exploration of a range of diagnostic and treatment strategies for the management of COVID-19 is the need of the hour.
Herein, Imiquimod (IMQ) was incorporated in nanotransethosomes (nTES) to develop the IMQ-nTES nano-drug delivery system. IMQ-nTES was optimized using 23 factorial design. The optimized formulation was expressed with a particle size of 192.4 ± 1.60 nm, Poly-dispersibility of 0.115 ± 0.008, and IMQ percent entrapment efficiency of 91.05 ± 3.22%. Smooth and round morphology of IMQ-nTES vesicles was confirmed by TEM micrographs. Moreover, FTIR results have shown drug-excipient compatibility. The IMQ-nTES was laden inside the low molecular weight chitosan gel, which exhibited easy application, spreadability and no irritation to the applied skin. The release pattern has clearly exhibited improved dissolution properties of IMQ with the provision of the sustain release pattern. Higher IMQ content was deposited in deeper epidermis and dermis with IMQ-nTES gel, in contrast to ALDARA. In vivo, comparative toxicity study on BALB/c mice has shown significantly reduced (p < 0.001) psoriatic area severity index (PASI) score and less increment in ear thickness. Epidermal hyperplasia was an obvious finding with ALDARA which was, providentially, minimal in IMQ-nTES gel-treated skin. FTIR analysis of skin tissue has shown an enhancement of lipid and protein content in the ALDARA group, however, in the IMQ-nTES group no such change was observed. With ALDARA application, CD4+ T-cells and constitutive NF-κβ expression were significantly elevated, in comparison to the IMQ-nTES gel treated group. Moreover, the adequate expression of IFN-γ and cytotoxic CD8+ T-cells were suggesting the preserved IMQ efficacy with IMQ-nTES gel. Quantification of cutaneous as well as systemic inflammatory markers has also suggested the reduced psoriatic potential of IMQ-nTES gel. In essence, IMQ-nTES gel can be a suitable alternative to ALDARA owing to its better safety profile.
Background The 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid isolated from the Tussilago farfara Linneaus (Asteraceae), was evaluated against acute Carrageenan and chronic complete Freund’s adjuvant (CFA)-induced arthritis in mice. Methods Acute and chronic arthritis were induced by administering Carrageenan and CFA to the intraplantar surface of the mouse paw. Edema, mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia were assessed in the paw. Similarly, histological and immunohistological parameters were assessed following arthritis induced by CFA. Antioxidants, inflammatory cytokines, and oxidative stress markers were also studied in all the treated groups. Results The ECN treatment significantly attenuated edema in the paw and elevated the nocifensive threshold following induction of this inflammatory model. Furthermore, ECN treatment markedly improved the arthritis index and distress symptoms, while attenuating the CFA-induced edema in the paw. ECN treatment also improved the histological parameters in the paw tissue compared to the control. At the same time, there was a significant reduction in edema and erosion in the ECN-treated group, as measured by radiographic analysis. Using the Comet’s assay, we showed that ECN treatment protected the DNA from chronic CFA-induced arthritis. Immunohistochemistry analysis showed a marked decrease in the expression level of p-JNK (phosphorylated C-Jun N-terminal kinase), NF-κB (Nuclear factor-kappa B), COX-2 (Cyclooxygenase-2), and TNF-α (Tumour necrosis factor-alpha) compared to the CFA-treated group. Biophysical analysis involving molecular docking, molecular dynamics simulations, and binding free energies of ECN were performed to explore the underlying mechanism. Conclusion ECN exhibited significant anti-inflammatory and anti-arthritic activity against Carrageenan and CFA-induced models.
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