Mechanism and potentialities of photothermal and photodynamic therapy of transition metal dichalcogenides (TMDCs) against cancer.

The ultimate goal of nanoparticle-based phototherapy is to suppress tumor growth. Photothermal therapy (PTT) and photothermal photodynamic therapy (PDT) are two types of physicochemical therapy that use light radiation with multiple wavelength ranges in the near-infrared to treat cancer. When a laser is pointed at tissue, photons are taken in the intercellular and intracellular regions, converting photon energy to heat. It has attracted much interest and research in recent years. The advent of transition materials dichalcogenides (TMDCs) is a revolutionary step in PDT/PTT-based cancer therapy. The TMDCs is a multilayer 2D nano-composite. TMDCs contain three atomic layers in which two chalcogens squash in the transition metal. The chalcogen atoms are highly reactive, and the surface characteristics of TMDCs help them to target deep cancer cells. They absorb Near Infrared (NIR), which kills deep cancer cells. In this review, we have discussed the history and mechanism of PDT/PTT and the use of TMDCs and nanoparticle-based systems, which have been practiced for theranostics purposes. We have also discussed PDT/PTT combined with immunotherapy, in which the cancer cell apoptosis is done by activating the immune cells, such as CD8+.

Enhanced Brain Delivery via Intranasal Administration of Carbamazepine Loaded Solid Lipid Nanoparticles: Optimization, Pharmacokinetic Analysis, In-vitro, and In-vivo Drug Release Study.

BACKGROUND: Carbamazepine (Cbz) is the first-line drug for epileptic seizures but exhibits fluctuation at the plasma level and side effects after oral administration.To overcome these problems, Cbz should be targeted directly into the brain. Therefore, the current experimental design was aimed to formulate and optimize the Cbz containing solid lipid nanoparticles (SLNs) for brain delivery via intranasal administration to get rid of oral complications associated with Cbz. METHODS: A full factorial design was performed to evaluate the effect of variables (X1 lipid concentration, X2 surfactant concentration, and X3 sonication time) on the response variables (size of nanoparticles, entrapment efficiency, and drug release). A two-level, three-factor design was employed herewith, and eight formulations were developed. Further, the formation of Cbz containing SLNs was characterized by compatibility, particle size, entrapment efficiency, and drug release with the support of Fourier Transform Infra-Red (FTIR), Zeta sizer, Transmission Electron Microscopy (TEM), Ultra-violet (U.V.), and High-Performance Liquid Chromatography (HPLC). RESULTS: All eight formulations were characterized through particle size, entrapment efficiency, and invitro drug release performance. Out of eight characterized formulations, SN1 showed the most promising results, including particle size of 210 ± 2.14 nm, entrapment efficiency of 42.1 ± 1.09%, and drug release of 61.3 ± 2.02% and considered an optimized batch. Additionally, the optimized batch SN1was further evaluated for an in-vivo study on male Wistar Rats. CONCLUSION: The study revealed that a high amount of drug was reached into the brain through intranasal administration compared to the intravenous route. Therefore, it can minimize the unwanted side effects of the Cbz associated with oral administration. The formulation SN1 possesses an excellent drug targeting efficiency of 3.014. Finally, the current experimental work concluded that there is a direct pathway from the intranasal route to the brain. This delivery system can be beneficial for directly delivering CNS-active drugs into the brain.

Silver Nanoparticles from Saudi and Syrian Black Cumin Seed Extracts: Green Synthesis, ADME, Toxicity, Comparative Research, and Biological Appraisal.

Objective: The current study's objective is to highlight the value of using plant resources to identify key bioactive molecules and implement green chemistry in research and development to meet market demand. Materials and Methods: The black cumin seeds (Saudi and Syria originated) were utilized to make silver nanoparticles (Ag-NPs), which were subsequently confirmed using a UV spectrophotometer and color analysis of reaction mixtures. The antibacterial activity of Ag-NPs was tested against E. coli, K. pneumoniae, and S. aureus, and antioxidant activity was measured using the DPPH assay. Swiss-ADME, pkCSM, and ProTox-II were also used to assess the pharmacokinetics, oral bioavailability, toxicity, and safety endpoints of molecules. Result: The antibacterial effect of Ag-NPs from Saudi-origin black cumin seeds was observed higher. In comparison to the standard, the Saudi and Syrian Ag-NPs combined displayed synergistic antibacterial effects and were found to be more susceptible to S. aureus. In comparison to the reference, the antioxidant activity of Ag-NPs indicated 60-85% radical scavenging. All molecules passed the Lipinski rule, the filter (Veber, Egan, and Muegge), PAINS, and the Brenk structural alert (zero violations), and the synthetic score was also found to be in the easy limit (1 to 2). The compounds were found to be non-substrate for p-glycoprotein, high GIA% (>90%), non-inhibitor for CYP3A4, CYP2C19, CYP2C9, CYP2D6 (except 5 and 10), Log Po/w (1.71 to 3.26), TPSA 150 2 and MR 155. The compounds likewise had high Caco2 values (log Papp >0.9) with the exception of 4 and 9 (log Papp 0.9), were non-inhibitors of P-gp-I and II and hERG I and II, and showed no AMES toxicity. Except for molecule 11, no organ damage (hepatotoxicity) or endpoint toxicity (mutagenicity, immunotoxicity, carcinogenicity, and cytotoxicity) was identified in ProTox-II. Conclusion: The current study sheds new light on the significance of bioactive molecules found in black cumin seeds, with molecules 3 and 6 identified as potential leads (highest GIA%, no AMES toxicity, oral rat acute and chronic toxicity, lack of renal OCT2 substrate, high total clearance, and lack of organ toxicity) for further research for a variety of medical applications.

Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.

Background: Glycyrrhiza glabra L. (G. glabra) commonly known as liquorice is one of the highly exploited and utilized medicinal plant of the world. Since ancient times liquorice is considered as an auspicious and valuable traditional medicine across the world for treatment of various ailments. Method: Several electronic online scientific databases such as Science Direct, PubMed, Scopus, Scifinder, Google Scholar, online books and reports were assessed for collecting information. All the collected information was classified into different sections to meet the objective of the paper. Results: The electronic database search yielded 3908 articles from different countries. Out of them one ninety-eight articles published between 1956 and 2021 were included, corresponding to all detailed review on G. glabra and research on anti-inflammatories, antivirals and immunomodulatory through pre-clinical and clinical models. From all selective area of studies on G. glabra and its bioactive components it was established (including molecular mechanisms) as a suitable remedy as per the current requirement of pandemic situation arise through respiratory tract infection. Conclusion: Different relevant studies have been thoroughly reviewed to gain an insight on utility of liquorice and its bioactive constituents for anti-inflammatories, antivirals and immunomodulatory effects with special emphasized for prevention and treatment of COVID-19 infection with possible mechanism of action at molecular level. Proposed directions for future research are also outlined to encourage researchers to find out various mechanistic targets and useful value added products of liquorice in future investigations.