Precision nanomedicine to treat non-small cell lung cancer.

Lung cancer is a major cause of death worldwide, being often detected at a later stage due to the non-appearance of early symptoms. Therefore, specificity of the treatment is of utmost importance for its effective treatment. Precision medicine is a personalized therapy based on the genomics of the patient to design a suitable drug approach. Genetic mutations render the tumor resistant to specific mutations and the therapy is in vain even though correct medications are prescribed. Therefore, Precision medicine needs to be explored for the treatment of Non-small cell lung cancer (NSCLC). Nanoparticles are widely explored to give personalized interventions to treat lung cancer due to their various advantages like the ability to reach cancer cells, enhanced permeation through tissues, specificity, increased bioavailability, etc. Various nanoparticles (NPs) including gold nanoparticles, carbon nanotubes, aptamer-based NPs etc. were conjugated with biomarkers/diagnostic agents specific to cancer type and were delivered. Various biomarker genes have been identified through precision techniques for the diagnosis and treatment of NSCLC like EGFR, RET, KRAS, ALK, ROS-1, NTRK-1, etc. By incorporating of drug with the nanoparticle through bioconjugation, the specificity of the treatment can be enhanced with this revolutionary treatment. Additionally, integration of theranostic cargos in the nanoparticle would allow diagnosis as well as treatment by targeting the site of disease progression. Therefore, to target NSCLC effectively precision nanomedicine has been adopted in recent times. Here, we present different nanoparticles that are used as precision nanomedicine and their effectiveness against NSCLC disease.

Development of Epigallocatechin 3-gallate-Loaded Hydrogel Nanocomposites for Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a chronic progressive disease associated with increased collagen deposition and TGF-ß1 release. The current therapy and management have been a limited success due to low efficacy and adverse drug reactions. This study aimed to evaluate epigallocatechin 3-gallate (EGCG) encapsulated nanoparticles loaded mucoadhesive hydrogel nanocomposite (HNC) for OSF. Developed HNC formulations were evaluated for their permeation behaviour using in vitro as well as ex vivo studies, followed by evaluation of efficacy and safety by in vivo studies using areca nut extract-induced OSF in rats. The disease condition in OSF-induced rats was assessed by mouth-opening and biochemical markers. The optimized polymeric nanoparticles exhibited the required particle size (162.93 ± 13.81 nm), positive zeta potential (22.50 ± 2.94 mV) with better mucoadhesive strength (0.40 ± 0.002 N), and faster permeation due to interactions of the positively charged surface with the negatively charged buccal mucosal membrane. HNC significantly improved disease conditions by reducing TGF-ß1 and collagen concentration without showing toxicity and reverting the fibroid buccal mucosa to normal. Hence, the optimized formulation can be further tested to develop a clinically alternate therapeutic strategy for OSF.

Recent advances in dual-drug co-amorphous systems.

Poor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited absorption because of their weak solubility and high permeability. Co-amorphous systems (CAMs) have been studied widely as a way to improve the solubility of drugs. This review summarizes recent advancements in dual-drug CAMs, including improvements in formulation, manufacturing, and solid-state characterization, and highlights the importance of enhancing solubility and stability. It emphasizes the potential synergistic effects of two drugs in CAMs and explores formulation strategies and challenges related to maintaining the amorphous state. Case studies demonstrate the successful application of CAMs in combination therapies that offer improved therapeutic efficacy.

Identification of potential Akt activators: a ligand and structure-based computational approach.

The Akt pathway plays a significant role in various diseases like Alzheimer's, Parkinson's, and Diabetes. Akt is the central protein whose phosphorylation controls many downstream pathways. Binding of small molecules to the PH domain of Akt facilitates its phosphorylation in the cytoplasm and upregulates the Akt pathway. In the current study, to identify Akt activators, ligand-based approaches like 2D QSAR, shape, and pharmacophore-based screening were used, followed by structure-based approaches such as docking, MM-GBSA, ADME prediction, and MD simulation. The top twenty-five molecules from the Asinex gold platinum database found to be active in most 2D QSAR models were used for shape and pharmacophore-based screening. Later docking was performed using the PH domain of Akt1 (PDB: 1UNQ), and 197105, 261126, 253878, 256085, and 123435 were selected based on docking score and interaction with key residues, which were druggable and formed a stable protein-ligand complex. MD simulations of 261126 and 123435 showed better stability and interactions with key residues. To further investigate the SAR of 261126 and 123435, derivatives were downloaded from PubChem, and structure-based approaches were employed. MD simulation of derivatives 12289533, 12785801, 83824832, 102479045, and 6972939 was performed, in which 83824832 and 12289533 showed interaction with key residues for a longer duration of time, proving that they may act as Akt activators.

Integrated LC-MS/MS and network pharmacology approach for predictingactive ingredients and pharmacological mechanisms of Tribulus terrestris L. against cardiac diseases.

Tribulus terrestris L. (Gokshura) is a medicinal herb used for treating cardiac diseases and several other diseases. However, the active ingredients and the possible mechanism of action for treating cardiac diseases remain unclear. Hence, the study was designed to identify the active ingredients and to explore the potential mechanism of action of Tribulus terrestris L. for treating cardiac diseases by an integrated approach of metabolomics and network pharmacology. We performed HPLC-QTOF-MS/MS analysis to identify putative compounds and network pharmacology approach for predictive key targets and pathways. Using molecular docking and molecular dynamics simulation, we identified the active ingredients in Tribulus terrestris L. that can act as putative lead compounds to treat cardiac diseases. A total of 55 putative compounds were identified using methanolic extract of Tribulus terrestris L. using HPLC-QTOF-MS/MS analysis. Network pharmacology analysis predicted 32 human protein targets from 25 secondary metabolites, which have shown direct interaction with cardiac diseases. Based on the degrees of interaction, the hub targets such as TACR1, F2, F2R, ADRA1B, CHRM5, ADRA1A, ADRA1D, HTR2B, and AVPR1A were identified. In silico molecular docking and simulation resulted in the identification of active ingredients such as Kaempferol 3-rutinoside 7-glucuronide, Keioside, rutin, moupinamide, aurantiamide, quercetin-3-o-α-rhamnoside, tribuloside, and 3'',6''- Di-O-p-coumaroyltrifolin against hub protein targets. Hence, these compounds could be potential lead compounds for treating cardiac diseases. A further assessment of its efficacy can be made based on in vivo and in vitro studies for better understanding and strong assertion.Communicated by Ramaswamy H. Sarma.

Polyphenol-based targeted therapy for oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico, in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-ß1), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-ß1, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-ß1 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects. Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-ß1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-ß1 and improved mouth opening in OSF rat model.

Identification of phytochemical as a dual inhibitor of PI3K and mTOR: a structure-based computational approach.

Breast cancer is a common form of cancer that affects both men and women. One of the most common types of genomic flaws in cancer is the aberrations in the PI3K/AKT/mTOR pathway. The benefit of dual targeting PI3K as well as mTOR is that the kinase-positive feedback loops are more effectively inhibited. Therefore, in the current study, structure-based models like molecular docking, MM-GBSA, Qikprop, induced fit docking, simulated molecular dynamics (MD), and thermal MM-GBSA were used to identify the phytochemicals from the zinc 15 database, which may inhibit PI3K and mTOR. After docking the phytochemicals with PI3K (PDB 4FA6), ten ligands based on the docking score were selected, among which salvianolic acid C had the highest docking score. Hence, salvianolic acid A was also docked. All the ligands taken showed a binding energy of greater than - 30 kcal/mol. The predicted ADME showed that the ligands have druggable properties. By performing MD of the top five ligands and salvianolic acid A, it was found that ZINC000059728582, ZINC000257545754, ZINC000253532301, and salvianolic acid A form a stable complex with PI3K protein, among which ZINC000014690026 showed interaction with Val 882 for more than 89% of the time. Salvianolic acid A is already proven to suppress tumor growth in acute myeloid leukemia by inhibiting PI3K/AKT pathway, but the exact protein target is unknown. Therefore, the present study identifies new molecules and provides evidence for salvianolic acid A for dual inhibition. Further experiments must be performed both in vitro and in vivo to support the predictions of these computational tools.

Drug-Carrier Miscibility in Solid Dispersions of Glibenclamide and a Novel Approach to Enhance Its Solubility Using an Effervescent Agent.

The present research aims to investigate the miscibility, physical stability, solubility, and dissolution rate of a poorly water-soluble glibenclamide (GLB) in solid dispersions (SDs) with hydrophilic carriers like PEG-1500 and PEG-50 hydrogenated palm glycerides (Acconon). Mathematical theories such as Hansen solubility parameters, Flory Huggins theory, Gibbs free energy, and the in silico molecular dynamics simulation study approaches were used to predict the drug-carrier miscibility. To increase the solubility further, the effervescence technique was introduced to the conventional solid dispersions to prepare effervescent solid dispersions (ESD). Solid dispersions (SDs) were prepared by microwave, solvent evaporation, lyophilization, and hot melt extrusion (HME) techniques and tested for different characterization parameters. The theoretical and in silico parameters suggested that GLB would show good miscibility with the selected carriers under certain conditions. Intermolecular hydrogen bonding between the drug and carrier(s) was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Solid-state characterizations like powder X-ray diffraction, differential scanning calorimetry, and microscopy confirm the amorphous nature of SDs. The addition of the effervescent agent improved the amorphous nature, due to which the solubility and drug release rate was increased. In vitro and ex vivo intestinal absorption studies showed improved flux and permeability than the pure drug, suggesting an enhanced drug delivery. The GLB solubility, dissolution, and stability were greatly enhanced by the SD and ESD technology.

Probing nonenzymatic glycation of proteins by deep ultraviolet light emitting diode induced autofluorescence.

The suitability of deep-UV-LED (285 nm) as an excitation source to induce autofluorescence in nonenzymatically glycated proteins has been reported for the first time in this study. Non-enzymatically glycated proteins show high autofluorescence when excited with deep-UV light, i.e., deep-UV-induced autofluorescence (deep-UV-IAF). Multiple autofluorescence peaks of nonenzymatically glycated proteins between 300 and 600 nm when excited using the deep-UV-LED revealed structural and biochemical modifications. The partial unfolding of proteins in which Tryptophan (Trp) is either absent (e.g., RibonucleaseA) or the emission maxima of Trp is insensitive to nonenzymatic glycation (e.g., Human Serum Albumin and Bovine Serum Albumin) were elucidated using their Tyrosine (Tyr) emission (λem = ~320 nm). Also, the deep-UV-LED-induced autofluorescence (deep-UV-LED-IAF) is shown to detect and track a wide range of clinically relevant advanced glycation end-products (AGEs) such as Pentosidine (λem = ~380 nm), Argpyrimidine (λem = ~395 nm), Vesperlysine C (λem = ~405 nm), Vesperlysine A/B (λem = ~440 nm), Crossline (λem = ~480 nm), and Arginine derived AGEs (λem = ~525 nm) which is also supported by the chemometric analysis (PCA). The relevance of Trp/Tyr makeup of proteins in tracking AGEs using deep-UV-IAF has been carefully examined with proteins such as RibonucleaseA (RNaseA:zero Trp and six Tyr), Human Serum Albumin (HSA: one Trp and eighteen Tyr), Bovine Serum Albumin (BSA: two Trp and twenty Tyr) and Hemoglobin (Hb: four Trp and twelve Tyr). The Molecular Dynamic (MD) simulation revealed a high root-mean-square deviation (RMSD: 4.6 Å) and an increased average distance between Tyr residues and Trp214 (23.2 Å) in methylglyoxal (MG) treated HSA. This confirms the MG-induced protein unfolding and decreased fluorescence resonance energy transfer (FRET) from Tyr to Trp (Tyr â†’ Trp). The study also used systematic steady-state and time-resolved fluorescence (TRF) to explain the sudden decrease in AGEs specific fluorescence intensity and lifetime at higher concentrations of MG due to inter-AGEs FRET.

Comparative Evaluation of the Effectiveness of a Combination of Absorbable Gelatin Sponge and Calendula officinalis with Absorbable Gelatin Sponge Used Alone as a Hemostatic Agent-An In-Vitro Study.

Excessive bleeding can complicate surgical intervention; this could be managed using an effective hemostatic agent that provides immediate and early bleeding control. Gelatin sponge and Calendula officinalis have been proven to have good hemostatic properties. The present In-vitro study analyzed the cytotoxicity and hemostatic properties of gelatin sponge and Calendula officinalis. The cytotoxic concentration/effective concentration of Calendula officinalis was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The drug release was determined using a vertical Franz diffusion cell apparatus; solid-state characterization was assessed using Fourier-transform infrared spectroscopy (FTIR) and a differential scanning calorimeter (DSC). The MTT assay showed 7% Calendula officinalis to be cytocompatible, and there was an increase in cell proliferation. When the 7% Calendula officinalis was loaded into the sponge, it was compatible, and the drug content was found to be 56.28 ± 13.84%. The time taken for the blood clot formation was measured using the Lee-White method. The gelatin sponge's time for clot formation was 161.70 ± 3.11 s, and the Calendula officinalis loaded gelatin sponge's time for clot formation was 158.75 ± 4.60 s. Hence, it could be concluded that when Calendula officinalis is incorporated into a gelatin sponge, it shows material compatibility and cytocompatibility, reduces the time for clot formation, and could be used as an alternative to other hemostatic agents.

Molecular pathways and role of epigenetics in the idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with unknown etiological factors that can progress to other dangerous diseases like lung cancer. Environmental and genetic predisposition are the two major etiological or risk factors involved in the pathology of the IPF. Among the environmental risk factors, smoking is one of the major causes for the development of IPF. Epigenetic pathways like nucleosomes remodeling, DNA methylation, histone modifications and miRNA mediated genes play a crucial role in development of IPF. Mutations in the genes make the epigenetic factors as important drug targets in IPF. Transcriptional changes due to environmental factors are also involved in the progression of IPF. The mutations in human telomerase reverse transcriptase (hTERT) have shown decreased life expectancy in IPF patients. The TERT-gene is highly expressed in chronic smokers and makes the role of epigenetics evident. Drug like nintedanib acts through vascular endothelial growth factor receptors (VEGFR), while drug pirfenidone acts through transforming growth factor (TGF), which is useful in IPF. Gefitinib, a tyrosine kinase inhibitor of EGFR, is useful as an anti-fibrosis agent in preclinical models. Newer drugs such as Celgene-CC90001 and FibroGen-FG-3019 are currently under investigations acts through the modulating epigenetic mechanisms. Thus, the study on epigenetics opens a wide window for the discovery of newer drugs. This study provides an elementary analysis of multiple regulators of epigenetics and their roles associated with the pathology of IPF. Further, this review also includes epigenetic drugs under development in preclinical and clinical stages.

The Beginning of a New Era: Artificial Intelligence in Healthcare.

The healthcare sector is considered to be one of the largest and fast-growing industries in the world. Innovations and novel approaches have always remained the prime aims in order to bring massive development. Before the emergence of technology, the healthcare sector was dependent on manpower, which was time-consuming and less accurate with lack of efficiency. With the recent advancements in machine learning, the condition has been steadily revolutionizing. Artificial intelligence (AI) lies in the computer science department, which stresses on the intelligent machines' creation, that work and react just like human beings. Currently, the applications of AI have been expanding into those fields, which was once thought to be the only domain of human expertise such as healthcare sector. In this review, we have shed light on the present usage of AI in the healthcare sector, such as its working, and the way this system is being implemented in different domains, such as drug discovery, diagnosis of diseases, clinical trials, remote patient monitoring, and nanotechnology. We have also briefly touched upon its applications in other sectors as well. The public opinions have also been analyzed and discussed along with the future prospects. We have discussed the merits, and the other side of AI, i.e. the disadvantages in the last part of the manuscript.

Implications of phase solubility/miscibility and drug-rich phase formation on the performance of co-amorphous materials: The case of Darunavir co-amorphous materials with Ritonavir and Indomethacin as co-formers.

The present study was designed to investigate the contribution of solid-state and the impact of composite drug-rich phase generated as a consequence of pH shift on the maximum achievable supersaturation of co-amorphous formulations. The co-amorphous phases of weak base-weak base-pair i.e. Ritonavir and Darunavir were prepared in anticipation of studying the effect of drug-rich phase consequent to pH shift. While the co-amorphous phases of weak base-Weak acid pair i.e. Darunavir and Indomethacin were studied to understand the manifestation of the solid-state drug: co-former miscibility in the absence of drug rich phase. Thermodynamically, the lowering of the supersaturation was found commensurate with the mole fraction of the respective component (Drug/Co-former) within the co-amorphous materials for both Darunavir: Ritonavir and Darunavir: Indomethacin pair. Kinetically, for Darunavir: Ritonavir co-amorphous materials, the shift in the pH from acidic to the neutral side led to the generation of drug-rich phase and subsequent LLPS. The free drug concentration achieved in the bulk of the solution was found dependent upon the mole fraction of the respective component within the drug-rich phase. The relative mole fraction of each component within the composite drug-rich phase is dictated by pH-dependent solubility and molecular weight of the individual components.

Chitosan-glucuronic acid conjugate coated mesoporous silica nanoparticles: A smart pH-responsive and receptor-targeted system for colorectal cancer therapy.

Glycosylated pH-sensitive mesoporous silica nanoparticles (MSNs) of capecitabine (CAP) were developed for targeting colorectal cancer. The MSNs possessed an average pore diameter of 8.12 ± 0.43 nm, pore volume of 0.73 ± 0.21 cm3/g, and particle size of 245.24 ± 5.75 nm. A high loading of 180.51 ± 5.23 mg/g attributed to the larger pore volume was observed. The surface of the drug-loaded MSNs were capped with chitosan-glucuronic acid (CHS-GCA) conjugate to combine two strategies viz. pH-sensitive, and lectin receptor mediated uptake. In vitro studies demonstrated a pH-sensitive and controlled release of CAP which was further enhanced in the presence of rat caecal content. Higher uptake of the (CAP-MSN)CHS-GCA was observed in HCT 116 cell lines. The glycosylated nanoparticles revealed reduction in the tumors, aberrant crypt foci, dysplasia and inflammation, and alleviation in the toxic features. This illustrated that the nanoparticles showed promising antitumor efficacy with reduced toxicity and may be used as a effective carrier against cancer.

Molecular docking, binding mode analysis, molecular dynamics, and prediction of ADMET/toxicity properties of selective potential antiviral agents against SARS-CoV-2 main protease: an effort toward drug repurposing to combat COVID-19.

The importance of the main protease (Mpro) enzyme of SARS-CoV-2 in the digestion of viral polyproteins introduces Mpro as an attractive drug target for antiviral drug design. This study aims to carry out the molecular docking, molecular dynamics studies, and prediction of ADMET properties of selected potential antiviral molecules. The study provides an insight into biomolecular interactions to understand the inhibitory mechanism and the spatial orientation of the tested ligands and further, identification of key amino acid residues within the substrate-binding pocket that can be applied for structure-based drug design. In this regard, we carried out molecular docking studies of chloroquine (CQ), hydroxychloroquine (HCQ), remdesivir (RDV), GS441524, arbidol (ARB), and natural product glycyrrhizin (GA) using AutoDock 4.2 tool. To study the drug-receptor complex's stability, selected docking possesses were further subjected to molecular dynamics studies with Schrodinger software. The prediction of ADMET/toxicity properties was carried out on ADMET Prediction™. The docking studies suggested a potential role played by CYS145, HIS163, and GLU166 in the interaction of molecules within the active site of COVID-19 Mpro. In the docking studies, RDV and GA exhibited superiority in binding with the crystal structure of Mpro over the other selected molecules in this study. Spatial orientations of the molecules at the active site of Mpro exposed the significance of S1-S4 subsites and surrounding amino acid residues. Among GA and RDV, RDV showed better and stable interactions with the protein, which is the reason for the lesser RMSD values for RDV. Overall, the present in silico study indicated the direction to combat COVID-19 using FDA-approved drugs as promising agents, which do not need much toxicity studies and could also serve as starting points for lead optimization in drug discovery.

Simvastatin in polymer bioscaffold for bone regeneration. An in vitro and in vivo analysis.

OBJECTIVE: The study aimed to fabricate and test the biocompatibility of a polylactic-co-glycolic acid (PLGA) based guided tissue regeneration membrane impregnated with 'simvastatin' to promote sustained drug delivery near osseous defects and evaluate the regenerative potential of the membrane histologically. MATERIALS AND METHODS: We tested the mechanical properties and cytotoxicity of an indigenously fabricated PLGA membrane incorporated with simvastatin (1 mg/cm2). An animal study evaluated the regenerative potential of the membrane. Twenty-four adult Wistar rats, approximately 175 g in weight, were used in this study. The rats were divided randomly into four groups based on the postoperative healing periods into ten days, 1, 3, and 6 months. Within each time group, six rats were divided into three subgroups: Subgroup A - sham surgery controls; Subgroup B - PLGA without Simvastatin; Subgroup C - PLGA with simvastatin tests. The radiographic examination intervals were ten days, 1 and 3 months, while the histological assessment was around 1, 3, and 6 months. RESULTS: Simvastatin content was distributed uniformly in all the prepared membranes and was equivalent to 1 mg/cm2. 100 mg PLGA membrane with simvastatin demonstrated uniform drug release over time, excellent mechanical properties, and biocompatibility. The rat models in Subgroup C had better bone tissue formation radiographically and histologically. CONCLUSION: The study suggested that 'PLGA with Simvastatin' has the requisite properties to serve as a third-generation barrier membrane with the potential for local drug delivery.

Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing.

The intricate biological process of cutaneous wound healing is achieved through precise and highly programmed events. Dermal fibroblasts and keratinocytes play a significant role in the process of reepithelialization during wound healing. Pathogenic bacteria such as Pseudomonas aeruginosa (P. aeruginosa) may delay the proliferative phase of wound repair by secreting their proteins leading to delayed or impaired wound healing. We have analyzed three virulent strains of P. aeruginosa isolated from the wound environment which also differed in their ability to produce biofilms. Mass spectrometric analysis of differentially expressed secreted proteins by three virulent strains of P. aeruginosa revealed peptides from pseudolysin and protease IV expressed from lasB and prpL genes. Pseudolysin and protease IV recombinant proteins were tested for their ability to modulate wound healing in several cell types of wound microenvironment in in vitro and in vivo models. Both pseudolysin and protease IV inhibited migration and survival of fibroblasts, keratinocytes, and endothelial cells. In three dimensional spheroid endothelial models and matrigel assays these proteins impeded sprouting and tube formation. In a mouse model of excision wound, pseudolysin and protease IV treatment showed reduced collagen content, inhibited neovascularization and epithelialization, and delayed wound contraction. Furthermore, pseudolysin and protease IV treatment resulted in a significant increase in plasma IL-6 levels when compared to vehicle control and control, suggesting the induction of a state of prolonged inflammation. Taken together, our data indicate pseudolysin and protease IV secreted from biofilm producing and antibiotic resistant P. aeruginosa in wound microenvironment produce both local and systemic effects that is detrimental to the maintenance of tissue homeostasis. Hence, these proteins may serve as potential therapeutic targets toward better clinical management of wounds.

Asphaltene Aggregation in Aqueous Solution Using Different Water Models: A Classical Molecular Dynamics Study.

The aggregation behavior of asphaltene in aqueous solution is systematically investigated based on a classical molecular dynamics study. In this work, a novel approach is adopted in order to investigate the structural and dynamical properties of the asphaltene nanoaggregates using different water models. The end-to-end distance of the asphaltene molecule is probed in order to understand the aggregation behavior in aqueous solution. The accuracy of different water models, that is, simple point charge, TIP4P-D, and TIP5P, is thoroughly investigated. In order to probe the dynamical properties of the asphaltene nanoaggregates, the transport coefficients, namely, diffusion coefficient and shear viscosity, are computed. The obtained results highlight the importance of using the appropriate water model in order to accurately study the aggregation behavior of asphaltene in aqueous solution.

Anti-aging and Sunscreens: Paradigm Shift in Cosmetics.

Skin, being one of the vital organs and a protective barrier needs to be pampered and taken care of from early childhood. It is the most visible and the widest exposed organ and by far reflects the general health condition and the aging process in humans. Both intrinsic and extrinsic factors contribute to this complex biological process of skin aging. In recent times, skin health and its beauty is perceived as an indicator of one's health which has resulted in an increasing demand for anti-aging products. Exposure to UV radiation is considered to be one of the factors responsible for aging termed as photoaging. In this review, we have discussed the various factors which may accelerate the process of skin aging. Various approaches and strategies to delay the process of skin aging have been emphasized upon. The patents filed in the area of anti-aging and sunscreen products have also been reviewed to gain an insight into the new formulations which have been developed as an anti-aging product. There has been a tremendous rise in the cosmetic and cosmeceuticals market with products having a dual activity of anti-aging and sun protection. Research is constantly on the rise to ensure the safety of these products. Alternatives to the current topical application of sunscreen are being considered to overcome the drawback of reapplication of the sunscreen often which can be a boon to the cosmeceutical market.

Localized In Situ Nanoemulgel Drug Delivery System of Quercetin for Periodontitis: Development and Computational Simulations.

This study was aimed at formulating a bioabsorbable, controlled-release, nanoemulgel of Quercetin, a potent antimicrobial and anti-inflammatory agent for the treatment of periodontitis that could improve its solubility and bioavailability. Screening of components was carried out based on the solubility studies. Nanoemulsion containing cinnamon oil as the oil phase, tween 80 and Carbitol® as the surfactant-cosurfactant mixture (Smix) and water as the aqueous phase containing 125 µg/200 µL of Quercetin was prepared by using spontaneous emulsification method. Nanoemulgel was prepared using 23% w/v poloxamer 407 as gel base. Comprehensive evaluation of the formulated nanoemulgel was carried out, and the optimized formulation was studied for drug release using Franz vertical diffusion cells. The formulated nanoemulgelexhibited a remarkable release of 92.4% of Quercetin at the end of 6 h, as compared to that of pure Quercetin-loaded gel (<3% release). The viscosity of the prepared nanoemulgel was found to be 30,647 ± 0.32 cPs at 37 °C. Also, molecular dynamics (MD) simulation was utilized to understand the gelation process and role of each component in the formulation. The present study revealed that the developed nanoemulgel of Quercetin could be a potential delivery system for clinical testing in periodontitis.