Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies.

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

Combinatorial delivery of Ribociclib and green tea extract mediated nanostructured lipid carrier for oral delivery for the treatment of breast cancer synchronising in silico, in vitro, and in vivo studies.

PURPOSE: The current research investigated the development and evaluation of dual drug-loaded nanostructure lipidic carriers (NLCs) of green tea extract and Ribociclib. METHOD: In silico study were performed to determine the effectiveness of combinational approach. The prepared NLCs were subjected to in vitro drug release, lipolysis, haemolysis and cell line studies to assess their in vivo prospect. RESULTS: In silico study was done to get docking score of EGCG (-8.98) close to Ribociclib (-10.78) in CDK-4 receptors. The prepared NLCs exhibited particle size (175.80 ± 3.51 nm); PDI (0.571 ± 0.012); and %EE [RBO (80.91 ± 1.66%) and GTE 75.98 ± 2.35%)] respectively. MCF-7 cell lines were used to evaluate the MTT assay, cellular uptake and antioxidant (ROS and SOD) of prepared NLCs. In vitro drug release showed the controlled release up to 72 h. In vitro lipolysis and in vitro haemolysis studies showed the availability of drugs at absorption sites and the greater in vivo prospects of NLCs respectively. Pharmacokinetic study revealed a 3.63-fold and 1.53-fold increment in RBO and GTE bioavailability in female Wistar rats respectively. CONCLUSION: The prominent potential of green tea extract and RBO-loaded NLCs in enhancing their therapeutic efficacy for better treatment of breast cancer.

An Overview of the Neuropharmacological Potential of Thymoquinone and its Targeted Delivery Prospects for CNS Disorder.

At present, people and patients worldwide are relying on the medicinal plant as a therapeutic agent over pharmaceuticals because the medicinal plant is considered safer, especially for chronic disorders. Several medicinal plants and their components are being researched and explored for their possible therapeutic contribution to CNS disorders. Thymoquinone (TQ) is one such molecule. Thymoquinone, one of the constituents of Plant Nigella Sativa, is effective against several neurodegenerative diseases like, Alzheimer's, Depression, Encephalomyelitis, Epilepsy, Ischemia, Parkinson's, and Traumatic. This review article presents the neuropharmacological potential of TQ's, their challenges, and delivery prospects, explicitly focusing on neurological disorders along with their chemistry, pharmacokinetics, and toxicity. Since TQ has some pharmacokinetic challenges, scientists have focused on novel formulations and delivery systems to enhance bioavailability and ultimately increase its therapeutic value. In the present work, the role of nanotechnology in neurodegenerative disease and how it improves the bioavailability and delivery of a drug to the site of action has been discussed. There are a few limitations to developing novel drug formulations, including solubility, pH, and compatibility of nanomaterials. Since here we are targeting CNS disorders, the bloodbrain barrier (BBB) becomes an additional challenge. Hence, the review summarized the novel aspects of delivery and biocompatible nanoparticles-based approaches for targeted drug delivery into CNS, enhancing TQ bioavailability and its neurotherapeutic effects.

ZnO Nanoparticles of Rubia cordifolia Extract Formulation Developed and Optimized with QbD Application, Considering Ex Vivo Skin Permeation, Antimicrobial and Antioxidant Properties.

The objective of the current research is to develop ZnO-Manjistha extract (ZnO-MJE) nanoparticles (NPs) and to investigate their transdermal delivery as well as antimicrobial and antioxidant activity. The optimized formulation was further evaluated based on different parameters. The ZnO-MJE-NPs were prepared by mixing 10 mM ZnSO4·7H2O and 0.8% w/v NaOH in distilled water. To the above, a solution of 10 mL MJE (10 mg) in 50 mL of zinc sulfate was added. Box-Behnken design (Design-Expert software 12.0.1.0) was used for the optimization of ZnO-MJE-NP formulations. The ZnO-MJE-NPs were evaluated for their physicochemical characterization, in vitro release activity, ex vivo permeation across rat skin, antimicrobial activity using sterilized agar media, and antioxidant activity by the DPPH free radical method. The optimized ZnO-MJE-NP formulation (F13) showed a particle size of 257.1 ± 0.76 nm, PDI value of 0.289 ± 0.003, and entrapment efficiency of 79 ± 0.33%. Drug release kinetic models showed that the formulation followed the Korsmeyer-Peppas model with a drug release of 34.50 ± 2.56 at pH 7.4 in 24 h. In ex vivo studies ZnO-MJE-NPs-opt permeation was 63.26%. The antibacterial activity was found to be enhanced in ZnO-MJE-NPs-opt and antioxidant activity was found to be highest (93.14 ± 4.05%) at 100 µg/mL concentrations. The ZnO-MJE-NPs-opt formulation showed prolonged release of the MJE and intensified permeation. Moreover, the formulation was found to show significantly (p < 0.05) better antimicrobial and antioxidant activity as compared to conventional suspension formulations.