Evaluation of the effect of precursor ratios on the electrochemical performances of binder-free NiMn-phosphate electrodes for supercapattery.

Binary metal phosphate electrodes have been widely studied for energy storage applications due to the synergistic effects of two different transition elements that able to provide better conductivity and stability. Herein, the battery-type binder-free nickel-manganese phosphate (NiMn-phosphate) electrodes were fabricated with different Ni:Mn precursor ratios via microwave-assisted hydrothermal technique for 5 min at 90 °C. Overall, NiMn3P electrode (Ni:Mn = 1:3) showed an outstanding electrochemical performance, displaying the highest specific (areal) capacity at 3 A/g of 1262.4 C/g (0.44 C/cm2), and the smallest charge transfer resistance of 108.8 Ω. The enhanced performance of NiMn3P electrode can be ascribed to the fully grown amorphous nature and small-sized flake and flower structures of NiMn3P electrode material on the nickel foam (NF) surface. This configuration offered a higher number of active sites and a larger exposed area, facilitating efficient electrochemical reactions with the electrolyte. Consequently, the NiMn3P//AC electrode combination was chosen to further investigate its performance in supercapattery. The NiMn3P//AC supercapattery exhibited remarkable energy density of 105.4 Wh/kg and excellent cyclic stability with 84.7% retention after 3000 cycles. These findings underscored the superior electrochemical performance of the battery-type binder-free NiMn3P electrode, and highlight its potential for enhancing the overall performance of supercapattery.

Investigating the adsorption potential of char derived from waste latex for methylene blue removal.

This study presents the adsorption of methylene blue (MB) dye using latex char derived from pyrolysis of latex gloves. The adsorption process was investigated systematically using Response Surface Methodology (RSM) with a Central Composite Design (CCD). The effects of four key variables, namely pH, time, temperature, and adsorbent dosage, were studied using a factorial design enriched with center points and axial points. Experimental data were analyzed using a second-order polynomial regression model to construct a response surface model, which elucidated the relationship between the variables and MB removal efficiency. The study found that the char obtained at 800°C exhibited the highest adsorption capacity due to its increased carbonization, expanded surface area, and diverse pore structure. Analysis of Variance (ANOVA) confirmed the significance of the quadratic model, with remarkable agreement between predicted and experimental outcomes. Diagnostic plots validated the model's reliability, while 3D contour graphs illustrated the combined effects of variables on MB removal efficiency. Optimization using DoE software identified optimal conditions resulting in a 99% removal efficiency, which closely matched experimental results. Additionally, adsorption isotherms revealed that the Freundlich model best described the adsorption behavior, indicating heterogeneous surface adsorption with multilayer adsorption. This comprehensive study provides valuable insights into the adsorption process of MB dye using latex char, with implications for wastewater treatment and environmental remediation.

Kenaf-based activated carbon: A sustainable solution for high-performance aqueous symmetric supercapacitors.

This study presents an innovative method for synthesizing activated carbon with an exceptionally high surface area (3359 m2 g-1) using kenaf fiber-based biochar through chemical activation. The achieved specific surface area surpasses activated carbon derived from other reported fiber-based precursors. The resulting activated carbon was investigated as electrodes for supercapacitors, revealing a remarkable maximum capacitance of 312 F g-1 at a current density of 0.5 A g-1. An aqueous symmetric supercapacitor employing these high-surface-area electrodes exhibited an outstanding energy density of 18.9 Wh kg-1 at a power density of 250 W kg-1. Notably, the supercapacitor retained exceptional capacitance, maintaining 93% of its initial capacitance even after 5000 charge-discharge cycles.

Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches.

Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM.

Advanced oxidation and biological integrated processes for pharmaceutical wastewater treatment: A review.

The stress of pharmaceutical and personal care products (PPCPs) discharging to water bodies and the environment due to increased industrialization has reduced the availability of clean water. This poses a potential health hazard to animals and human life because water contamination is a great issue to the climate, plants, humans, and aquatic habitats. Pharmaceutical compounds are quantified in concentrations ranging from ng/Lto µg/L in aquatic environments worldwide. According to (Alsubih et al., 2022), the concentrations of carbamazepine, sulfamethoxazole, Lutvastatin, ciprofloxacin, and lorazepam were 616-906 ng/L, 16,532-21635 ng/L, 694-2068 ng/L, 734-1178 ng/L, and 2742-3775 ng/L respectively. Protecting and preserving our environment must be well-driven by all sectors to sustain development. Various methods have been utilized to eliminate the emerging pollutants, such as adsorption and biological and advanced oxidation processes. These methods have their benefits and drawbacks in the removal of pharmaceuticals. Successful wastewater treatment can save the water bodies; integrating green initiatives into the main purposes of actor firms, combined with continually periodic awareness of the current and potential implications of environmental/water pollution, will play a major role in water conservation. This article reviews key publications on the adsorption, biological, and advanced oxidation processes used to remove pharmaceutical products from the aquatic environment. It also sheds light on the pharmaceutical adsorption capability of adsorption, biological and advanced oxidation methods, and their efficacy in pharmaceutical concentration removal. A research gap has been identified for researchers to explore in order to eliminate the problem associated with pharmaceutical wastes. Therefore, future study should focus on combining advanced oxidation and adsorption processes for an excellent way to eliminate pharmaceutical products, even at low concentrations. Biological processes should focus on ideal circumstances and microbial processes that enable the simultaneous removal of pharmaceutical compounds and the effects of diverse environments on removal efficiency.

Impact of UV radiation on Mxene-mediated tubulin dissociation and mitochondrial apoptosis in breast cancer cells.

Breast cancer is a global health concern that requires personalized therapies to prevent relapses, as conventional treatments may develop resistance over time. Photothermal therapy using spectral radiation or intense light emission is a broad-spectrum treatment that induces hyperthermia-mediated cancer cell death. MXene, a two-dimensional material, has been reported to have potential biological applications in photothermal therapy for cancer treatment. In this study, we investigated the apoptotic activity of MXene and UV-irradiated MXene in MCF-7 breast cancer cells by treating them with varying concentrations of MXene. The cytotoxicity of MXene and UV was evaluated by analyzing cellular morphology, nuclei condensation, caspase activation, and apoptotic cell death. We also assessed the effect of the combined treatment on the expression and cellular distribution of Tubulin, a key component of microtubules required for cell division. At low concentrations of MXene (up to 100 µg/ml), the level of cytotoxicity in MCF-7 cells was low. However, the combined treatment of MXene and UV resulted in a synergistic increase in cytotoxicity, causing rounded cellular morphology, condensed nuclei, caspase activation, and apoptotic cell death. Furthermore, the treatment reduced Tubulin protein expression and cellular distribution, indicating a potent inducer of cell death with potential application for cancer treatment. The study demonstrates that the combined treatment of MXene and UVB irradiation is a promising strategy for inducing apoptotic cell death in breast cancer cells, suggesting its potential as a therapeutic intervention for breast cancer.

Corrigendum: Stylopine: a potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy.

[This corrects the article DOI: 10.3389/fphar.2023.1150270.].

In-silico evaluation of Bismurrayaquinone-A phytochemical as a potential multifunctional inhibitor targeting dihydrofolate reductase: implications for anticancer and antibacterial drug development.

Dihydrofolate reductase (DHFR) has gained significant attention in drug development, primarily due to marked distinctions in its active site among different species. DHFR plays a crucial role in both DNA and amino acid metabolism by facilitating the transfer of monocarbon residues through tetrahydrofolate, which is vital for nucleotide and amino acid synthesis. This considers its potential as a promising target for therapeutic interventions. In this study, our focus was on conducting a virtual screening of phytoconstituents from the IMPPAT2.0 database to identify potential inhibitors of DHFR. The initial criterion involved assessing the binding energy of molecules against DHFR and we screened top 20 compounds ranging energy -13.5 to -11.4 (kcal/Mol) while Pemetrexed disodium bound with less energy -10.2 (kcal/Mol), followed by an analysis of their interactions to identify more effective hits. We prioritized IMPHY007679 (Bismurrayaquinone-A), which displayed a high binding affinity and crucial interaction with DHFR. We also evaluated the drug-like properties and biological activity of IMPHY007679. Furthermore, MD simulation was done, RMSD, RMSF, Rg, SASA, PCA and FEL explore the time-evolution impact of IMPHY007679 comparing it with a reference drug, Pemetrexed disodium. Collectively, our findings suggest that IMPHY007679 recommend further investigation in both in vitro and in vivo settings for its potential in developing anticancer and antibacterial therapies. This compound holds promise as a valuable candidate for advancing drug research and treatment strategies.Communicated by Ramaswamy H. Sarma.

In vivo assessment of black seed oil single dose on prednisolone pharmacokinetics.

OBJECTIVES: To investigate the effect of blackseed oil (BSO) single dose on prednisolone pharmacokinetics via p-gp inhibition. METHODS: Three groups of rats (n = 5) were orally administered the vehicle, verapamil (50 mg/kg) or BSO (5 ml/kg) 15 min prior to prednisolone (5 mg/kg) administration. Blood samples were collected over 24 h and quantified. Non-compartmental analysis was employed to calculate maximum plasma concentration (Cmax), area under the curve (AUC0-last), time to reach Cmax (Tmax), apparent clearance (CL/F), and half-life (t1/2). Statistical significance was considered at p<0.05. RESULTS: Prednisolone Cmax and AUC0-last decreased by 65% and 25% in the BSO group compared to the negative control (P < .0001, .0029, respectively) while they increased by 1.75-folds and 8-folds in verapamil group (P < .0001). Tmax was achieved at 0.16, 0.5, and 0.25 h in the negative control, verapamil, and BSO-treated groups, respectively. CL/F in the treatment group was 1.3-fold and 10-fold higher compared to the negative and positive control, respectively, whereas the t1/2 remained comparable. CONCLUSION: Administration of BSO decreased prednisolone Cmax and AUC0-last in rats indicating that there is a herb-drug interaction; however, p-gp inhibition cannot be concluded. Patients relying on folk medicine in chronic illnesses treatment might need to avoid combining BSO with prednisolone.

Microwave-assisted upcycling of plastic waste to high-performance carbon anode for lithium-ion batteries.

The increasing demand for high-performance lithium-ion batteries (LIBs) has emphasized the need for affordable and sustainable materials, prompting the exploration of waste upcycling to address global sustainability challenges. In this study, we efficiently converted polypropylene (PP) plastic waste from used centrifuge tubes into activated polypropylene carbon (APC) using microwave-assisted pyrolysis. The synthesis of APC was optimized using response surface methodology/central composite design (RSM/CCD). Based on the RSM results, the optimal conditions for PP plastic conversion into carbon were determined as follows: HNO3 concentration of 3.5 M, microwave temperature of 230 °C, and holding time of 25 min. Under these conditions, the obtained intensity ratio of Id/Ig in PP carbon was 0.681 ± 0.013, with an error of 6.81 ± 0.013 % between predicted and actual values. The physicochemical studies, including FESEM-EDX, XRD, and Raman spectroscopy, confirmed the successful synthesis of APC samples. The APC 800 material exhibited a well-organized three-dimensional structure characterized by large pores and mesopores, enabling fast ion transport in the electrode. As a result, the APC 800 electrode demonstrated an initial discharge capacity of 381.0 mAh/g, an improved initial coulombic efficiency of 85.1%, and excellent cycling stability after 100 cycles. Notably, the APC 800 electrode displayed remarkable rate performance, showing a reversible capacity of 355.1 mAh/g when the current density was reset to 0.2 A/g, highlighting its high electrochemical reversibility. The outstanding characteristics of APC 800 as an anode electrode material for high-performance lithium-ion batteries suggest a promising future for its application in the field.

Distant entanglement via photon hopping in a coupled cavity magnomechanical system.

We theoretically propose a scheme to generate distant bipartite entanglement between various subsystems in coupled magnomechanical systems where both the microwave cavities are coupled through single photon hopping coupling strength Γ. Each cavity contains a magnon mode and phonon mode and this gives six excitation modes in our model Hamiltonian which are cavity-1 photons, cavity-2 photons, magnon and phonon in cavity-1, and magnon and phonon in cavity-2. We found that significant bipartite entanglement exists between indirectly coupled subsystems in coupled microwave cavities for an appropriate set of parameters regime. Moreover, we also obtain suitable cavity and magnon detuning parameters for a significant distant bipartite entanglement in different bipartitions. In addition, it can be seen that a single photon hopping parameter significantly affects both the degree as well as the transfer of quantum entanglement between various bipartitions. Hence, our present study related to coupled microwave cavity magnomechanical configuration will open new perspectives in coherent control of various quantum correlations including quantum state transfer among macroscopic quantum systems.

Targeting CDK6 in hormone receptor-positive breast cancer: inhibitor discovery for precision oncology through dynamics study.

CDK6 is a critical protein involved in the regulation of the cell cycle, playing an important role in the progression from the G1 to S phase. In breast cancer, dysregulation of this protein is involved in tumour development and progression, particularly in hormone receptor-positive (HR+) breast cancers. The upregulation of CDK6 have been observed in a subset of breast cancers, leading to uncontrolled progression of the cell cycle and increased proliferation of cells. The purpose of this abstract is to provide an outline of CDK6's role. In breast cancer and the therapeutic strategies targeting CDK6 using specific selected inhibitors. To discover viable therapeutic candidates after competitive inhibition of CDK6 with a small molecular drug complex, high throughput screening and docking studies were used. Further, we carried the compounds based on ADMET properties and prediction of activity spectra for substances analysis. Finally, two different compounds were selected to carry out MD simulations. CDK6-IMPHY002642 and CDK6-IMPHY005260 are the two compounds that were identified. Overall, our results suggest that the CDK6-IMPHY002642 and CDK6-IMPHY005260 complex was relatively stable during the simulation. The compounds that have been found can also be further examined as potential therapeutic possibilities. The combined findings suggest that CDK6, together with their genetic changes, can be investigated in therapeutic interventions for precision oncology, leveraging early diagnostics and target-driven therapy.Communicated by Ramaswamy H. Sarma.

Structure-based molecular docking and molecular dynamics simulations study for the identification of dipeptidyl peptidase 4 inhibitors in type 2 diabetes.

Inhibition of dipeptidyl peptidase-4 (DPP4) activity has emerged as a promising therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM). Bioinformatics-driven approaches have emerged as crucial tools in drug discovery. Molecular docking and molecular dynamics (MD) simulations are effective tools in drug discovery, as they reduce the time and cost associated with experimental screening. In this study, we employed structure-assisted in-silico methods, including molecular docking and MD simulations, to identify SRT2183, a small molecule that may potentially inhibit the activity of DPP4 enzyme. The interaction between the small molecule "SRT2183" and DPP4 exhibited a binding affinity of -9.9 Kcal/Mol, leading to the formation of hydrogen bonds with the amino acid residues MET348, SER376, and THR351 of DPP4. The MD simulations over a period of 100 ns indicated stable protein-ligand interactions, with no significant conformational rearrangements observed within the simulated timeframe. In conclusion, our results suggest that the small molecule SRT2183 may have the potential to inhibit the DPP4 enzyme and pave the way for the therapeutics of T2DM.Communicated by Ramaswamy H. Sarma.

Niosomes gel of apigenin to improve the topical delivery: development, optimization, ex vivo permeation, antioxidant study, and in vivo evaluation.

Niosomes (NS) are the promising and novel carrier of the drug for effective transdermal delivery. Apigenin (AN) is a natural bioactive compound and has various pharmacological activities. AN is poorly water soluble which directly affects therapeutic efficacy. The aim of this research work was to develop the AN-NS gel to improve transdermal delivery. The thin-film hydration method was used for the development of AN-NS. The optimized AN-NS (AN-NS2) has a vesicle size of 272.56 ± 12.49 nm, PDI is 0.249, zeta potential is -38.7 mV, and entrapment efficiency of 86.19 ± 1.51%. The FTIR spectra of the AN-NS2 depicted that AN encapsulated in the NS matrix. AN-NS2 formulation was successfully incorporated into chitosan gel and evaluated. The optimized AN-NS2 gel (AN-NS2G4) has 2110 ± 14cps of viscosity, 10.40 ± 0.21g.cm/sec of spreadability, and 99.65 ± 0.53% of drug content. AN-NS2G4 displayed significantly (p < 0.05) higher AN released (67.64 ± 3.03%) than pure AN-gel (37.31 ± 2.87%). AN-NS2G4 showed the Korsmeyer Peppas release model. AN-NS2G4 displayed significantly (p < 0.05) higher antioxidant activity (90.72%) than pure AN (64.53%) at 300 µg/ml. AN-NS2G4 displayed significantly (p < 0.05) higher % inhibition of swelling than pane AN-gel in carrageenin-induced paw oedema in rats. The finding concluded that niosomes-laden gel is a good carrier of drugs to improve transdermal delivery and therapeutic efficacy.

Prediction of molecular interaction of Phosphodiesterase 10A inhibition by natural compounds: insights from structure-based screening and molecular dynamics simulations.

Phosphodiesterase 10 A (PDE10A) is an enzyme that regulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in the brain, particularly in the striatum, which plays a critical role in movement control and reward processing. Inhibition of PDE10A can increase cAMP and cGMP levels, improving neuronal signaling and reducing symptoms of neuropsychiatric disorders such as schizophrenia, Huntington's disease, and Parkinson's disease. In this study, a structure-based virtual screening was conducted to identify potential anti-neuropsychiatric disorders compounds from phytoconstituents in the IMPPAT database. The ligands were docked against PDE10A, resulting in 40 compounds with appreciable docking scores. These 40 compounds underwent further ADMET predictions and drug likeliness, resulting in five potential compounds. Finally, based on the specific interactions, two compounds (Colladonin and Isopongachromene), were subjected to molecular dynamics (MD) simulation and MM-PBSA studies. The MM-PBSA analysis validated and captured the intermolecular interactions, indicating that Colladonin and Isopongachromene had appreciable binding affinities of -155.60 kJ.mol-1 and -108.28 kJ.mol-1, respectively and were promising candidates against neuropsychiatric disorders, targeting PDE10A. Overall, this study provides insight into the potential of PDE10A inhibitors as therapeutic agents for treating neuropsychiatric disorders, and Colladonin and Isopongachromene are promising compounds for further development.Communicated by Ramaswamy H. Sarma.

Enhanced tribological properties of diesel-based engine oil through synergistic MoS2-graphene nanohybrid additive.

This research explores the potential of microwave-synthesized MoS2-graphene nanohybrid as additives to enhance the tribological properties of diesel-based engine oil. The synthesis method offers significant advantages, reducing both synthesis time and energy consumption by 90-98% compared to conventional approaches. The synthesized nanohybrids are characterized through FESEM, EDX, XRD, and Raman spectroscopy to understand their morphology and functional group interactions. These nanohybrids are incorporated into 20W40 engine oil following synthesis, and a comprehensive assessment of their properties is conducted. This evaluation covers critical parameters like viscosity index, stability, volatility, as well as tribological properties, oxidation resistance, and thermal conductivity of the oil-nanohybrid system. Results demonstrate that adding just 0.05 wt% of MoS2-graphene nanohybrid leads to a remarkable 58.82% reduction in friction coefficient and a significant 36.26% decrease in the average wear scar diameter. Additionally, oxidation resistance improves by 19.21%, while thermal conductivity increases notably by 19.83% (at 100 °C). The study demonstrates the synergistic effects of these nanohybrids in reducing friction and wear, enhancing oxidation resistance, and improving thermal conductivity. In conclusion, this research highlights the potential of microwave-synthesized MoS2-graphene nanohybrid as promising tribological additives for diesel engine oils. Their successful integration could significantly enhance the performance and durability of critical mechanical components in diesel engines, representing a significant advancement in lubrication technology.

Discovery of promising B lymphocyte kinase inhibitors using structure-guided virtual screening.

Tyrosine-protein kinase BLK, also known as B-cell lymphocyte kinase (BLK), is a non-receptor tyrosine kinase that is primarily expressed in B-cells. BLK plays a key role in B-cell signaling, particularly in B-cell development and maturation. The increased expression of BLK has been linked to various complex diseases, including autoimmune disorders, and specific malignancies of B cells, such as lymphomas and leukemias. Due to its significant involvement in B-cell signaling, BLK has emerged as a promising target for drug development, offering the potential for developing novel therapeutics to combat these diseases. Small molecule inhibitors of BLK hold great potential for therapeutic intervention; however, discovering potent and selective inhibitors remains challenging. Within this context, natural compounds hold significant potential as a valuable resource for discovering novel inhibitors of BLK. In the current study, a structure-based virtual screening of the IMPPAT 2 library was employed to identify promising candidates with potential as inhibitors of BLK. The control molecule for this study was the known BLK inhibitor, Dasatinib. After a multi-step filtering process, two molecules (Withanolide I and Mexogenin) demonstrated potential against BLK based on their superior binding affinity, ligand efficiency, and specific interaction. Interaction analysis of these compounds revealed several significant interactions with the active site residues of BLK. Both proposed molecules remained bound to the binding pocket of BLK, as indicated by the molecular dynamics (MD) simulation study. Taken together, these findings provide valuable insights for guiding future research endeavors and translational efforts in developing therapeutics for different complex diseases, such as autoimmune disorders, lymphomas, and leukemias.Communicated by Ramaswamy H. Sarma.

Optimization of chromatographic conditions via Box‒Behnken design in RP-HPLC-PDA method development for the estimation of folic acid and methotrexate in bulk and tablets.

Simultaneous estimation of folic acid and methotrexate in bulk and tablet dosage form by RP-HPLC-PDA was conducted via Box‒Behnken design application. Three-factor numerical values were finalized from the graphical and numerical optimization with built-in ANOVA in BBD. Sharp and symmetric peaks were observed at 4.138 and 6.929 min for folic acid and methotrexate, respectively. The mobile phase composition was methanol and 0.1% formic acid in water with a ratio of 31:69 and a flow rate of 1.1 ml/min. Both drugs were detected at a wavelength of 291 nm. The developed method was validated according to ICH guidelines. The results of the validation parameters were within acceptable limits. Stress stability studies have been performed under acidic, alkali, oxidation, neutral and photolytic conditions. Three different brand-marketed tablets were assessed with the developed method (MGXT, FOLTNAX and TRUXOFOL). In the tablet formulations, chromatogram percentages of folic acid and methotrexate were calculated at 99.13% and 99.50 in MGXT, 99.17% and 99.47 in FOLTNAX, and 99.91 and 100.05 in TRUXOFOL.

Hypophyllanthin and Phyllanthin from Phyllanthus niruri Synergize Doxorubicin Anticancer Properties against Resistant Breast Cancer Cells.

Doxorubicin (DOX) is a cornerstone chemotherapeutic agent for the treatment of several malignancies such as breast cancer; however, its activity is ameliorated by the development of a resistant phenotype. Phyllanthus species have been studied previously for their potential anticancer properties. The current work is aimed to study the potential cytotoxicity and chemomodulatory effects of hypophyllanthin (PN4) and phyllanthin (PN5) isolated from Phyllanthus niruri to DOX against the adriamycin multidrug-resistant breast cancer cells (MCF-7ADR) and elucidate their mechanism of action. The major compounds of the active methylene chloride fraction were isolated and assessed for their potential cytotoxicity and chemomodulatory effects on DOX against naïve (MCF-7) and resistant breast (MCF-7ADR) cancer cells. The mechanism of action of both compounds in terms of their impacts on programmed/non-programmed cell death (apoptosis and autophagy/necrosis), cell cycle progression/arrest, and tumor cell migration/invasion was investigated. Both compounds PN4 and PN5 showed a moderate but similar potency against MCF-7 as well as MCF-7ADR and significantly synergized DOX-induced anticancer properties against MCF-7ADR. The chemomodulatory effect of both compounds to DOX was found to be via potentiating DOX-induced cell cycle interference and apoptosis induction. It was found that PN4 and PN5 blocked the apoptosis-escape autophagy pathway in MCF-7ADR. On the molecular level, both compounds interfered with SIRT1 expression and consequently suppressed Akt phosphorylation, and PN5 blocked apoptosis escape. Furthermore, PN4 and PN5 showed promising antimigratory and anti-invasive effects against MCF-7ADR, as confirmed by suppression of N-cadherin/ß-catenin expression. In conclusion, for the first time, hypophyllanthin and phyllanthin isolated from P. niruri showed promising chemomodulatory effects to the DOX-induced chemotherapeutic activity against MCF-7ADR. Both compounds significantly synergized DOX-induced anticancer properties against MCF-7ADR. This enhanced activity was explained by further promoting DOX-induced apoptosis and suppressing the apoptosis-escape autophagy feature of the resistant breast cancer cells. Both compounds (hypophyllanthin and phyllanthin) interfered with the SIRT1/Akt pathway and suppressed the N-cadherin/ß-catenin axis, confirming the observed antiproliferative, cytotoxic, and anti-invasive effects of hypophyllanthin and phyllanthin.

Development of Soft Luliconazole Invasomes Gel for Effective Transdermal Delivery: Optimization to In-Vivo Antifungal Activity.

Luliconazole (LZ) is a good candidate for the treatment of fungal infection topically but has limitations, i.e., poor solubility and poor permeability to skin. Due to these limitations, multiple administrations for a long time are required to treat the inflection. The aim of the present study was to develop the invasomes (IVS) gel of LZ to improve the topical antifungal activity. The IVS was prepared by the thin-film hydration method and optimized by Box-Bhekhen design software. The optimized LZIVS (LZIVSopt) has 139.1 ± 4.32 nm of vesicle size, 88.21 ± 0.82% of entrapment efficiency, 0.301 ± 0.012 of PDI, and 19.5 mV (negative) of zeta potential. Scanning microscopy showed a spherical shape of the vesicle. FTIR spectra showed there is no interaction between the drug and lipid. Thermogram showed that the LZ is encapsulated into the LZIVS matrix. LZIVSopt gel (LZIVSopt-G3) exhibited optimum viscosity (6493 ± 27 cps) and significant spreadability (7.2 g·cm/s). LZIVSopt-G3 showed 2.47-fold higher permeation than pure LZ-gel. LZIVSopt-G3 did not show any edema or swelling in the skin, revealing that the developed formulation is non-irritant. LZIVSopt-G3 exhibited significant inhibition of the fungus infection (C. albicans) in the infected rats. The finding concluded that IVS gel is a good carrier and an attractive approach for the enhancement of topical delivery of LZ to treat the fungal infection.