Novel thymohydroquinone gallate (THQG) derivative loaded ligand Modified quantum dots as pH-Sensitive Multi-Modal theragnostic agent for cancer treatment.

BACKGROUND: Nanomedicine, as the combination of radiopharmaceutical and nanocarrier (QDs), is developed for treating cancer. Gallic acid is antimutagenic, anti-inflammatory, and anti-carcinogenic. Typical retention time of gallic acid is approximately 4 to 8 h. To increase the retention time gallic acid is converted to prodrug by adding lipophilic moieties, encapsulating in lipophilic nanoparticles, or liposome formation. Similarly, thymoquinone is powerful antioxidant, anti-apoptotic, and anti-inflammatory effect, with reduced DNA damage. METHODS: In this study, a hydrophilic drug (gallic acid) is chemically linked to the hydrophobic drug (thymohydroquinone) to overcome the limitations of co-delivery of drugs. Thymohydroquinone (THQG) as the combination of gallic acid (GA) and thymoquinone (THQ) is loaded onto the PEI functionalized antimonene quantum dots (AM-QDs) and characterized by FTIR, UV-visible spectroscopy, X-ray powder diffraction, Zeta sizer, SEM and AFM, in-vitro and in-vivo assay, and hemolysis. RESULTS: The calculated drug loading efficiency is 90 %. Drug release study suggests the drug combination is pH sensitive and it can encounters acidic pH, releasing the drug from the nanocarrier. The drug and drug-loaded nanocarrier possesses low cytotoxicity and cell viability on MCF-7 and Cal-27 cell lines. The proposed drug delivery system is radiolabeled with Iodine-131 (131I) and Technetium (99mTc) and its deposition in various organs of rats' bodies is examined by SPECT-CT and gamma camera. Hemolytic activity of 2, 4, 6, and 8 µg/ml is 1.78, 4.16, 9.77, and 15.79 %, respectively, reflecting low levels of hemolysis. The system also sustains oxidative stress in cells and environment, decreasing ROS production to shield cells and keep them healthy. CONCLUSIONS: The results of this study suggest that the proposed drug carrier system can be used as a multi-modal theragnostic agent in cancer.

Nutritional and medicinal plants as potential sources of enzyme inhibitors toward the bioactive functional foods: an updated review.

Enzymes are biologically active complex protein molecules that catalyze most chemical reactions in living organisms, and their inhibitors accelerate biological processes. This review emphasizes medicinal food plants and their isolated chemicals inhibiting clinically important enzymes in common diseases. A mechanistic overview was investigated to explain the mechanism of these food bases enzyme inhibitors. The enzyme inhibition potential of medicinal food plants and their isolated substances was searched in Ovid, PubMed, Science Direct, Scopus, and Google Scholar. Cholinesterase, amylase, glucosidase, xanthine oxidase, tyrosinase, urease, lipoxygenase, and others were inhibited by crude extracts, solvent fractions, or isolated pure chemicals from medicinal food plants. Several natural compounds have shown tyrosinase inhibition potential, including quercetin, glabridin, phloretin-4-O-ß-D-glucopyranoside, lupinalbin, and others. Some of these compounds' inhibitory kinetics and molecular mechanisms are also discussed. Phenolics and flavonoids inhibit enzyme activity best among the secondary metabolites investigated. Several studies showed flavonoids' significant antioxidant and anti-inflammatory activities, highlighting their medicinal potential. Overall, many medicinal food plants, their crude extracts/fractions, and isolated compounds have been studied, and some promising compounds depending on the enzyme have been found. Still, more studies are recommended to derive potential pharmacologically active functional foods.

Evaluation of sustained-release in-situ injectable gels, containing naproxen sodium, using in vitro, in silico and in vivo analysis.

The study aimed to fabricate naproxen sodium loaded in-situ gels of sodium alginate. Different in-situ gel forming solutions of naproxen sodium and sodium alginate were prepared and gel formation was studied in different physiological ions i.e., CaCl2 and Ca-gluconate. The prepared gel formulations were evaluated for different physical attributes such as gelation time, sol-gel fraction, ATR-FTIR spectroscopy and in silico molecular dynamics (MD) simulations. Drug release studies were carried out in a dialysis membrane using USP dissolution basket apparatus-I. In vivo anti-inflammatory studies were performed in Sprague-Dawley rats having carrageenan-induced hind paw inflammation. Higher polymer concentration in formulations resulted in decreased gelation time and an increased gel fraction. The ATR-FTIR and MD simulation revealed H-bonding between the alginate and naproxen sodium at 3500-3200 cm-1 with a RMSD of ∼2.8 Å and binding free energy ΔGpred (GB) = -10.93 kcal/mol. In vitro drug release studies from F8CAG suggested a sustained release of naproxen sodium. In vivo studies revealed a continuous decrease in swelling degree (≈-5.28 ± 0.210 mm) in inflamed hind paw of Sprague-Dawley rats over 96 h. The in-situ gel forming injectable preparation (F8CAG) offers a sustained release of naproxen sodium in the articular cavity which promises the treatment of chronic inflammatory conditions such as arthritis.