Development of Stable Liposomal Drug Delivery System of Thymoquinone and Its In Vitro Anticancer Studies Using Breast Cancer and Cervical Cancer Cell Lines.

Thymoquinone, a well-known phytoconstituent derived from the seeds of Nigella sativa, exhibits unique pharmacological activities However, despite the various medicinal properties of thymoquinone, its administration in vivo remains challenging due to poor aqueous solubility, bioavailability, and stability. Therefore, an advanced drugdelivery system is required to improve the therapeutic outcome of thymoquinone by enhancing its solubility and stability in biological systems. Therefore, this study is mainly focused on preparing thymoquinone-loaded liposomes to improve its physicochemical stability in gastric media and its performance in different cancer cell line studies. Liposomes were prepared using phospholipid extracted from egg yolk. The liposomal nano preparations were evaluated in terms of hydrodynamic diameter, zeta potential, microscopic analysis, and entrapment efficiency. Cell-viability measurements were conducted using breast and cervical cancer cell lines. Optimized liposomal preparation exhibited polygonal, globule-like shape with a hydrodynamic diameter of less than 260 nm, PDI of 0.6, and zeta potential values of -23.0 mV. Solid-state characterizations performed using DSC and XRPD showed that the freeze-dried liposomal preparations were amorphous in nature. Gastric pH stability data showed no physical changes (precipitation, degradation) or significant growth in the average size of blank and thymoquinone-loaded liposomes after 24 h. Cell line studies exhibited better performance for thymoquinone-loaded liposomal drug delivery system compared with the thymoquinone-only solution; this finding can play a critical role in improving breast and cervical cancer treatment management.

Liposomal Drug Delivery of Blumea lacera Leaf Extract: In-Vivo Hepatoprotective Effects.

BACKGROUND: Blumea lacera (B. lacera) is a herbaceous plant commonly found in south-east Asia. It shows significant therapeutic activities against various diseases. The objectives of this study were to evaluate hepatoprotective effects of Blumea lacera leaf extract and also to investigate the comparative effectiveness between a liposomal preparation and a suspension of B. lacera leaf extract against carbon tetrachloride (CCl4)-induced liver damage. METHODS: B. lacera leaf extract was characterized using a GC-MS method. A liposomal preparation of B. lacera leaf extract was developed using an ethanol injection method and characterized using dynamic light scattering (DLS) and electronic microscopic systems. The hepatoprotective effects of B. lacera leaf extracts and its liposomal preparation were investigated using CCl4-induced liver damage in Long Evan rats. RESULTS: GC-MS data showed the presence of different components (e.g., phytol) in the B. lacera leaf extract. DLS and microscopic data showed that a liposomal preparation of B. lacera leaf extracts was in the nano size range. In vivo study results showed that liposomal preparation and a suspension of B. lacera leaf extract normalized liver biochemical parameters, enzymes and oxidative stress markers which were elevated due to CCl4 administration. However, a liposomal formulation of B. lacera leaf extract showed significantly better hepatoprotective effects compared to a suspension of leaf extract. In addition, histopathological evaluation showed that B. lacera leaf extract and its liposomal preparation treatments decreased the extent of CCl4-induced liver inflammations. CONCLUSION: Results demonstrated that B. lacera leaf extract was effective against CCl4-induced liver injury possibly due to the presence of components such as phytol. A liposomal preparation exhibited significantly better activity compared to a B. lacera suspension, probably due to improved bioavailability and stability of the leaf extract.

Preparation and Optimization of PEGylated Nano Graphene Oxide-Based Delivery System for Drugs with Different Molecular Structures Using Design of Experiment (DoE).

Graphene oxide (GO), due to its 2D planar structure and favorable physical and chemical properties, has been used in different fields including drug delivery. This study aimed to investigate the impact of different process parameters on the average size of drug-loaded PEGylated nano graphene oxide (NGO-PEG) particles using design of experiment (DoE) and the loading of drugs with different molecular structures on an NGO-PEG-based delivery system. GO was prepared from graphite, processed using a sonication method, and functionalized using PEG 6000. Acetaminophen (AMP), diclofenac (DIC), and methotrexate (MTX) were loaded onto NGO-PEG particles. Drug-loaded NGO-PEG was then characterized using dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), XRD. The DLS data showed that the drug-loaded NGO-PEG suspensions were in the size range of 200 nm-1.3 µm. The sonication time and the stirring rate were found to be the major process parameters which affected the average size of the drug-loaded NGO-PEG. FTIR, DSC, XRD, and SEM demonstrated that the functionalization or coating of the NGO occurred through physical interaction using PEG 6000. Methotrexate (MTX), with the highest number of aromatic rings, showed the highest loading efficiency of 95.6% compared to drugs with fewer aromatic rings (diclofenac (DIC) 70.5% and acetaminophen (AMP) 65.5%). This study suggests that GO-based nano delivery systems can be used to deliver drugs with multiple aromatic rings with a low water solubility and targeted delivery (e.g., cancer).

The growing complexity of COVID-19 drug and vaccine candidates: challenges and critical transitions.

COVID-19 has nowadays affected almost all our societies and global health systems. The latest deadly pandemic has heavily influenced both life and livelihood worldwide. SARS-CoV-2 is the causative organism of COVID-19, that is spreading and infecting significantly higher compared to other coronavirus, due to its constant mutation characteristics. At present although several extensive clinical trials are ongoing, neither approved drug therapy nor any vaccine are available to safely fight SARS-CoV-2. However, a progressive race among numerous research groups to discover a radical cure for the COVID-19 is under way. This review aims to provide an updated insight of the current research, development and trials on repurposing existing drugs and preventive intervention for COVID-19, along with the related issues, complexities and challenges, especially after the observed high transmissibility lately.

Liposomal drug delivery of Corchorus olitorius leaf extract containing phytol using design of experiment (DoE): In-vitro anticancer and in-vivo anti-inflammatory studies.

Phytol, a pharmacologically active compound present in Corchorus olitorius leaf exhibit a range of activity including anti-inflammatory, antioxidant, anticancer, hepatoprotective etc. However, phytol is poorly soluble and absorbed through the intestine wall, therefore the aim of this study is to develop liposomal drug delivery of Corchorus olitorius leaf extract with an average particle size below 150 nm and drug loading efficiency of ≥ 85 %. The impact of different process parameters and material attributes were studied on the average particle size and polydispersity of liposomal batches using design of experiment (DoE). Corchorus olitorius leaf extraction was performed using maceration method and characterised using GC-MS. Liposomal batches of Corchorus olitorius leaf extract were characterized using Malvern zetasizer, transmission electron microscopy (TEM) and UV spectroscopy. The in-vivo anti-inflammatory study of the liposomal preparation of phytol was evaluated using a rat model and in-vitro cancer cell line study was performed on AML and Leukamia cell lines. GC-MS study data showed that phytol is present in C. olitorius leaf extract. Process parameters and material attributes perspective processing temperature, buffer pH and drug: lipid ratio is found as major parameters affecting the average particle size and PDI value of liposomes. Liposomes were prepared in the range of 80-250 nm and optimized batches of liposomes showed drug entrapment efficiency of 60-88 %. In-vivo anti-inflammatory study showed significant activity for C. olitorius leaf extract against carrageenan induced paw edema, which is significantly increased while delivered through liposomes. In-vitro cancer cell line study data suggests that liposomal delivery of phytol was more active at lower concentration compared to pure phytol, for specific cell lines.

Analysis of a "3-(Naphthalen-1-ylimino) Indoline-2-one" compound and Its Antimicrobial Assessment Using Lipid-based Self-nanoemulsifying Formulations.

In recent years, indole derivatives have acquired conspicuous significance due to their wide spectrum of biological activities-antibacterial, antiviral, and anticonvulsant. This compound is derived from naturally grown plants. Therefore, synthesis of a novel "3-(Naphthalen-1-ylimino) indoline-2-one" compound (2) and its analysis using UPLC systems along with antimicrobial assessment was the aim of the current study. Isatin was used as a parent drug for synthesizing compound (2). Liquid Chromatographic analysis was performed using a C18 BEH column (1.7 µm 2.1 × 50 mm) by UPLC systems. Degradation studies were carried out to see whether acid, base, thermal, and oxidizing agents had any impact on the synthesized molecule in stress conditions (100 °C). A lipid-based self-nanoemulsifying formulation was developed and selectivity, specificity, recovery, accuracy, and precision were measured as part of the UPLC system's validation process. Antimicrobial studies were conducted using gram-positive and gram-negative bacteria. The standard samples were run with a concentration range of 5.0-100.0 µg/mL using the isocratic mobile phase comprising of methanol/water (70/30 %v/v) at 234 nm; good linearity (R2 = 0.9998) was found. The lower limits of detection (LOD) and quantitation (LOQ) of the method were found to be 0.81 µg/mL and 2.5 µg/mL, respectively. The coefficients of variation were found to be less than 2%. The antimicrobial study suggests that compound (2) has a substantial growth effect against gram-negative bacteria. It was successfully synthesized and applied to measure the concentrations in lipid-based dosage form, along with potent antimicrobial activities.

Antibacterial activities of green tea crude extracts and synergistic effects of epigallocatechingallate (EGCG) with gentamicin against MDR pathogens.

Plant extracts and their purified compounds were examined for synergistic antimicrobial activity using selected multi-drug resistant (MDR) pathogens. The study aims to investigate the antibacterial activity of green tea (Camellia sinensis) and its purified compound epigallocatechingallate (EGCG). The synergistic relation of the compound with antibiotic was detected against selected potential Gram positive and Gram negative pathogens. Staphylococcus aureus and Escherichia coli were used as test pathogens which were resistant to different groups of antibiotics. After collection of fresh green tea leaves, samples were washed and air dried. EGCG is one of the bioactive compounds and was separated from tea plant. Antibacterial activity of EGCG and crude extracts of green tea were done by microdilution method (minimum inhibitory concentration and minimum bactericidal concentration). The synergistic effect of EGCG and gentamicin was determined. MIC value of green tea extract was found at 125 µg/mL in case of MDR E. coli, MDR S. aureus and their reference strains and MBC at 500 µg/mL against S. aureus. No MBC value was found against E. coli. EGCG showed better activity on Gram positive pathogen compared to that of Gram negative. MBC value of this compound was 1250 µg/mL for E. coli where 625 µg/mL for S. aureus. Strong synergistic relation (FICI 0.325) was found against pathogens in the combination of EGCG with gentamycin. The purified EGCG compound of green tea has great synergistic effect against MDR pathogens. More investigation is needed to know the inhibitory effect of these plant extracts and their components.

Prediction of the mechanical behaviour of crystalline solids.

PURPOSE: To explore the use of crystal inter-planar d-spacings and slip-plane interaction energies for predicting and characterising mechanical properties of crystalline solids. METHODS: Potential relationships were evaluated between mechanical properties and inter-planar d-spacing, inter-planar interaction energy, and dispersive surface energy as determined using inverse gas chromatography (IGC) for a set of pharmaceutical materials. Inter-planar interaction energies were determined by molecular modelling. RESULTS: General trends were observed between mechanical properties and the largest inter-planar d-spacing, inter-planar interaction energies, and IGC dispersive surface energy. A number of materials showed significant deviations from general trends. Weak correlations and outliers were rationalised. CONCLUSIONS: Results suggest that the highest d-spacing of a material could serve as a first-order indicator for ranking mechanical behaviour of pharmaceutical powders, but with some reservation. Inter-planar interaction energy normalised for surface area shows only a weak link with mechanical properties and does not appear to capture essential physics of deformation. A novel framework linking mechanical properties of crystals to the distinct quantities, slip-plane energy barrier and inter-planar interaction (detachment) energy is proposed.