Oleogels: Versatile Novel Semi-Solid System for Pharmaceuticals.

Oleogels is a novel semi-solid system, focusing on its composition, formulation, characterization, and diverse pharmaceutical applications. Due to their stability, smoothness, and controlled release qualities, oleogels are frequently utilized in food, cosmetics, and medicinal products. Oleogels are meticulously formulated by combining oleogelators like waxes, fatty acids, ethyl cellulose, and phytosterols with edible oils, leading to a nuanced understanding of their impact on rheological characteristics. They can be characterized by methods like visual inspection, texture analysis, rheological measurements, gelation tests, and microscopy. The applications of oleogels are explored in diverse fields such as nutraceuticals, cosmetics, food, lubricants, and pharmaceutics. Oleogels have applications in topical, transdermal, and ocular drug delivery, showcasing their potential for revolutionizing drug administration. This review aims to enhance the understanding of oleogels, contributing to the evolving landscape of pharmaceutical formulations. Oleogels emerge as a versatile and promising solution, offering substantial potential for innovation in drug delivery and formulation practices.

Polymeric functionalization of mesoporous silica nanoparticles: Biomedical insights.

Mesoporous silica nanoparticles (MSNs) endowed with polymer coatings present a versatile platform, offering notable advantages such as targeted, pH-controlled, and stimuli-responsive drug delivery. Surface functionalization, particularly through amine and carboxyl modification, enhances their suitability for polymerization, thereby augmenting their versatility and applicability. This review delves into the diverse therapeutic realms benefiting from polymer-coated MSNs, including photodynamic therapy (PDT), photothermal therapy (PTT), chemotherapy, RNA delivery, wound healing, tissue engineering, food packaging, and neurodegenerative disorder treatment. The multifaceted potential of polymer-coated MSNs underscores their significance as a focal point for future research endeavors and clinical applications. A comprehensive analysis of various polymers and biopolymers, such as polydopamine, chitosan, polyethylene glycol, polycaprolactone, alginate, gelatin, albumin, and others, is conducted to elucidate their advantages, benefits, and utilization across biomedical disciplines. Furthermore, this review extends its scope beyond polymerization and biomedical applications to encompass topics such as surface functionalization, chemical modification of MSNs, recent patents in the MSN domain, and the toxicity associated with MSN polymerization. Additionally, a brief discourse on green polymers is also included in review, highlighting their potential for fostering a sustainable future.

Formulation and assessment of biological properties of garcinia indica fruit extract mouthrinse as an adjunct to oral hygiene regimen: an in vitro analysis.

The prevalence of gingivitis is substantial within the general population, necessitating rigorous oral hygiene maintenance. OBJECTIVE: This study assessed a Garcinia indica (GI) fruit extract-based mouthrinse, comparing it to a 0.1% turmeric mouthrinse and a 0.2% Chlorhexidine (CHX) mouthrinse. The evaluation encompassed substantivity, staining potential, antimicrobial efficacy and cytocompatibility. METHODOLOGY: The study employed 182 tooth sections. For antimicrobial analysis, 64 extracted human teeth coated with a polymicrobial biofilm were divided into four groups, each receiving an experimental mouthrinse or serving as a control group with distilled water. Microbial reduction was assessed through colony forming units (CFU). Substantivity was evaluated on 54 human tooth sections using a UV spectrophotometer, while staining potential was examined on 64 tooth sections. Cytocompatibility was tested using colorimetric assay to determine non-toxic levels of 0.2% GI fruit extract, 0.1% Turmeric, and 0.2% CHX. RESULTS: Data were analysed with one-way ANOVA (α=0.05). Cell viability was highly significant (p<0.001) in the 0.2% GI group (64.1±0.29) compared to 0.1% Turmeric (40.2±0.34) and 0.2% CHX (10.95±1.40). For antimicrobial activity, both 0.2% GI (20.18±4.81) and 0.2% CHX (28.22±5.41) exhibited no significant difference (P>0.05) at end of 12 hours. However, 0.1% Turmeric showed minimal CFU reduction (P<0.001). Substantivity results at 360 minutes indicated statistically significant higher mean release rate in 0.1%Turmeric (12.47±5.84 ) when compared to 0.2% GI (5.02±3.04) and 0.2% CHX (4.13±2.25) (p<0.001). The overall discoloration changes (∆E) were more prominent in the 0.2% CHX group (18.65±8.3) compared to 0.2% GI (7.61±2.4) and 0.1% Turmeric (7.32±4.9) (P<0.001). CONCLUSION: This study supports 0.2% GI and 0.1% Turmeric mouth rinses as potential natural alternatives to chemical mouth rinses. These findings highlight viability of these natural supplements in oral healthcare.

Design of floating formulations and antiulcer activity of Desmostachya bipinnata.

The study aims to design and optimize the floating formulations of the aqueous extract of Desmostachya bipinnata (ADB) to treat peptic ulcers. The trial concentrations of HPMC E50, HPMC K4M, and Carbopol 940 were used as factors, and floating lag time, total floating time, and % drug release at 12 h were used as responses. The formulation underwent evaluation for different parameters: aspirin-induced ulcers in rats assessed the antiulcer activity, and X-ray studies in rabbits evaluated the gastroretentive nature. The optimized formulation has shown a floating lag time of 32 s and floated in the gastric medium for more than 9 h with a maximum drug release of 93% at the end of 12 h by following the Korsmeyer-Peppas drug release mechanism. The optimized formulation has good flow properties. The FT-IR, DSC, and XRD studies show ADB and excipients didn't show any incompatibility. The formulation has shown significant antiulcer activity against aspirin-induced ulcers in rats, with an ulcer index of 3.38 ± 0.24 and inhibition of 76.67 ± 0.56%. The in vivo X-ray imaging proved the gastric retention of the formulations for more than 8 h. The results of the formulations demonstrate the floating ability and sustained drug release of the tablet responsible for treating peptic ulcers to show a localized effect in the gastric region and to maintain the ROS levels.

In-silico lead identification of the pan-mutant IDH1 and IDH2 inhibitors to target glioblastoma.

Glioblastoma (GBM) is an aggressive malignant type of brain tumor. Targeting one single intracellular pathway might not alleviate the disease, rather it activates the other molecular pathways that lead to the worsening of the disease condition. Therefore, in this study, we attempted to target both isocitrate dehydrogenase 1 (IDH1) and IDH2, which are one of the most commonly mutated proteins in GBM and other cancer types. Here, standard precision and extra precision docking, IFD, MM-GBSA, QikProp, and molecular dynamics (MD) simulation were performed to identify the potential dual inhibitor for IDH1 and IDH2 from the enamine database containing 59,161 ligands. Upon docking the ligands with IDH1 (PDB: 6VEI) and IDH2 (PDB: 6VFZ), the top eight ligands were selected, based on the XP Glide score. These ligands produced favourable MMGBSA scores and ADME characteristics. Finally, the top four ligands 12953, 44825, 51295, and 53210 were subjected to MD analysis. Interestingly, 53210 showed maximum interaction with Gln 277 for 99% in IDH1 and Gln 316 for 100% in IDH2, which are the crucial amino acids for the inhibitory function of IDH1 and IDH2 to target GBM. Therefore, the present study attempts to identify the novel molecules which could possess a pan-inhibitory action on both IDH1 and IDH that could be crucial in the management of GBM. Yet further evaluation involving in vitro and in vivo studies is warranted to support the data in our current study.Communicated by Ramaswamy H. Sarma.

Co-delivery of lapatinib and 5-fluorouracil transfersomes using transpapillary iontophoresis for breast cancer therapy.

Combination chemotherapy, involving the intervention of two or more anti-neoplastic agents has been the cornerstone in breast cancer treatment, owing to the applications it holds in contrast to the mono-therapy approach. This research predominantly focussed on proving the synergy between Lapatinib (LPT) and 5-Fluorouracil (5-FU) and further enhancing its localized permeation via transfersome-loaded delivery and iontophoresis to treat breast tumors. The IC50 values for LPT and 5-FU were found to be 19.38 µg/ml and 5.7 µg/ml respectively and their synergistic effect was proven by the Chou-Talalay assay using CompuSyn software. Furthermore, LPT and 5-FU were encapsulated within transfersomes and administered via the transpapillary route. The drug-loaded carriers were characterized for their particle size, polydispersity index, zeta potential, and entrapment efficiency. The ex vivo rat skin permeation studies indicated that when compared to LPT dispersion and 5-FU solution, drug-loaded transfersomes exhibited better permeability and their transpapillary permeation was enhanced on using iontophoresis. Moreover, both LPT and 5-FU transfersomes were found to be stable for 3 months when stored at a temperature of 5 ± 3 °C. The results indicated that this treatment strategy could be an effective approach in contrast to some of the conventional treatments employed to date.

Formulation and assessment of biological properties of garcinia indica fruit extract mouthrinse as an adjunct to oral hygiene regimen: an in vitro analysis

Abstract The prevalence of gingivitis is substantial within the general population, necessitating rigorous oral hygiene maintenance. Objective This study assessed a Garcinia indica (GI) fruit extract-based mouthrinse, comparing it to a 0.1% turmeric mouthrinse and a 0.2% Chlorhexidine (CHX) mouthrinse. The evaluation encompassed substantivity, staining potential, antimicrobial efficacy and cytocompatibility. Methodology The study employed 182 tooth sections. For antimicrobial analysis, 64 extracted human teeth coated with a polymicrobial biofilm were divided into four groups, each receiving an experimental mouthrinse or serving as a control group with distilled water. Microbial reduction was assessed through colony forming units (CFU). Substantivity was evaluated on 54 human tooth sections using a UV spectrophotometer, while staining potential was examined on 64 tooth sections. Cytocompatibility was tested using colorimetric assay to determine non-toxic levels of 0.2% GI fruit extract, 0.1% Turmeric, and 0.2% CHX. Results Data were analysed with one-way ANOVA (α=0.05). Cell viability was highly significant (p<0.001) in the 0.2% GI group (64.1±0.29) compared to 0.1% Turmeric (40.2±0.34) and 0.2% CHX (10.95±1.40). For antimicrobial activity, both 0.2% GI (20.18±4.81) and 0.2% CHX (28.22±5.41) exhibited no significant difference (P>0.05) at end of 12 hours. However, 0.1% Turmeric showed minimal CFU reduction (P<0.001). Substantivity results at 360 minutes indicated statistically significant higher mean release rate in 0.1%Turmeric (12.47±5.84 ) when compared to 0.2% GI (5.02±3.04) and 0.2% CHX (4.13±2.25) (p<0.001). The overall discoloration changes (∆E) were more prominent in the 0.2% CHX group (18.65±8.3) compared to 0.2% GI (7.61±2.4) and 0.1% Turmeric (7.32±4.9) (P<0.001). Conclusion This study supports 0.2% GI and 0.1% Turmeric mouth rinses as potential natural alternatives to chemical mouth rinses. These findings highlight viability of these natural supplements in oral healthcare.

A computational-based approach to fabricate Ceritinib co-amorphous system using a novel co-former Rutin for bioavailability enhancement.

In this study, we used molecular simulations to design Ceritinib (CRT) co-amorphous materials (CAMs) with concurrent improvement in solubility and bioavailability. Computational modeling enabled us to select the co-former by estimating the binding energy and intermolecular interactions. Rutin (RTH) was selected as a co-former for CRT CAMs using the solvent evaporation method to anticipate simultaneous improvement of solubility and bioavailability. The solid state characterization using DSC, XRPD, FT-IR, and a significant shift in Gordon Taylor experimental Tg values of co-amorphous materials revealed single amorphous phase formation and intermolecular interactions between CRT and RTH. The co-amorphous materials exhibited physical stability for up to 4 months under dry conditions (40 °C). Further, co-amorphous materials maintained the supersaturation for 24 hrs and improved solubility as well as dissolution of CRT. CRT:RTH 1:1 CAMs improved the permeability of CRT by 2 fold, estimated by employing the everted gut sac method. The solubility advantage of CAMs was also reflected in pharmacokinetic parameters, with a 3.1-fold and 2-fold improvement of CRT:RTH 2:1 in CRT exposure (AUC 0-t) and plasma concentration (Cmax) compared to the physical mixture, respectively.

Transforming Wound Management: Nanomaterials and Their Clinical Impact.

Wound healing is a complex process that can be further complicated in chronic wounds, leading to prolonged healing times, high healthcare costs, and potential patient morbidity. Nanotechnology has shown great promise in developing advanced wound dressings that promote wound healing and prevent infection. The review article presents a comprehensive search strategy that was applied to four databases, namely Scopus, Web of Science, PubMed, and Google Scholar, using specific keywords and inclusion/exclusion criteria to select a representative sample of 164 research articles published between 2001 and 2023. This review article provides an updated overview of the different types of nanomaterials used in wound dressings, including nanofibers, nanocomposites, silver-based nanoparticles, lipid nanoparticles, and polymeric nanoparticles. Several recent studies have shown the potential benefits of using nanomaterials in wound care, including the use of hydrogel/nano silver-based dressings in treating diabetic foot wounds, the use of copper oxide-infused dressings in difficult-to-treat wounds, and the use of chitosan nanofiber mats in burn dressings. Overall, developing nanomaterials in wound care has complemented nanotechnology in drug delivery systems, providing biocompatible and biodegradable nanomaterials that enhance wound healing and provide sustained drug release. Wound dressings are an effective and convenient method of wound care that can prevent wound contamination, support the injured area, control hemorrhaging, and reduce pain and inflammation. This review article provides valuable insights into the potential role of individual nanoformulations used in wound dressings in promoting wound healing and preventing infections, and serves as an excellent resource for clinicians, researchers, and patients seeking improved healing outcomes.

Controlled Release Technologies for Chronotherapy: Current Status and Future Perspectives.

The expression "as sure as night follows a day" emulates those certain cycles in the environment that are always stable. Circadian rhythms are a group of processes that occur within the body in synchronisation with the external factors in a 24 h cycle. Changes in lifestyle and work shifts have disrupted these stable rhythms, which is a leading cause of lifestyle diseases. Associations between these biological clocks and diseases are abundant. However, it is also known that certain drugs work more efficiently and have minimum toxicity when given during a particular phase of the circadian cycle. Chronotherapeutics focuses on treating diseases according to the endogenous processes which mediate xenobiotic metabolism and drug response at a cellular level. Therefore, treatment of those diseases that show aggravation of symptoms according to the circadian rhythms at a particular time is highly beneficial by chronotherapy. In this article, we have emphasised how the changes in rhythms caused diseases and how chronotherapeutic approaches such as controlled drug release technologies can be a better option for these circadian manipulations that seem to influence all types of disease conditions.

Computational drug repurposing of Akt-1 allosteric inhibitors for non-small cell lung cancer.

Non-small cell lung carcinomas (NSCLC) are the predominant form of lung malignancy and the reason for the highest number of cancer-related deaths. Widespread deregulation of Akt, a serine/threonine kinase, has been reported in NSCLC. Allosteric Akt inhibitors bind in the space separating the Pleckstrin homology (PH) and catalytic domains, typically with tryptophan residue (Trp-80). This could decrease the regulatory site phosphorylation by stabilizing the PH-in conformation. Hence, in this study, a computational investigation was undertaken to identify allosteric Akt-1 inhibitors from FDA-approved drugs. The molecules were docked at standard precision (SP) and extra-precision (XP), followed by Prime molecular mechanics-generalized Born surface area (MM-GBSA), and molecular dynamics (MD) simulations on selected hits. Post XP-docking, fourteen best hits were identified from a library of 2115 optimized FDA-approved compounds, demonstrating several beneficial interactions such as pi-pi stacking, pi-cation, direct, and water-bridged hydrogen bonds with the crucial residues (Trp-80 and Tyr-272) and several amino acid residues in the allosteric ligand-binding pocket of Akt-1. Subsequent MD simulations to verify the stability of chosen drugs to the Akt-1 allosteric site showed valganciclovir, dasatinib, indacaterol, and novobiocin to have high stability. Further, predictions for possible biological interactions were performed using computational tools such as ProTox-II, CLC-Pred, and PASSOnline. The shortlisted drugs open a new class of allosteric Akt-1 inhibitors for the therapy of NSCLC.

Identification of structural scaffold from interbioscreen (IBS) database to inhibit 3CLpro, PLpro, and RdRp of SARS-CoV-2 using molecular docking and dynamic simulation studies.

A novel coronavirus SARS-CoV-2 has caused a worldwide pandemic and remained a severe threat to the entire human population. Researchers worldwide are struggling to find an effective drug treatment to combat this deadly disease. Many FDA-approved drugs from varying inhibitory classes and plant-derived compounds are screened to combat this virus. Still, due to the lack of structural information and several mutations of this virus, initial drug discovery efforts have limited success. A high-resolution crystal structure of important proteins like the main protease (3CLpro) that are required for SARS-CoV-2 viral replication and polymerase (RdRp) and papain-like protease (PLpro) as a vital target in other coronaviruses still presents important targets for the drug discovery. With this knowledge, scaffold library of Interbioscreen (IBS) database was explored through molecular docking, MD simulation and postdynamic binding free energy studies. The 3D docking structures and simulation data for the IBS compounds was studied and articulated. The compounds were further evaluated for ADMET studies using QikProp and SwissADME tools. The results revealed that the natural compounds STOCK2N-00385, STOCK2N-00244, and STOCK2N-00331 interacted strongly with 3CLpro, PLpro, and RdRp, respectively, and ADMET data was also observed in the range of limits for almost all the compounds with few exceptions. Thus, it suggests that these compounds may be potential inhibitors of selected target proteins, or their structural scaffolds can be further optimized to obtain effective drug candidates for SARS-CoV-2. The findings of in-silico data need to be supported by in-vivo studies which could shed light on understanding the exact mode of inhibitory action.Communicated by Ramaswamy H. Sarma.

Multi-Targeting Approach in Selection of Potential Molecule for COVID-19 Treatment.

The coronavirus disease (COVID-19) is a pandemic that started in the City of Wuhan, Hubei Province, China, caused by the spread of coronavirus (SARS-CoV-2). Drug discovery teams around the globe are in a race to develop a medicine for its management. It takes time for a novel molecule to enter the market, and the ideal way is to exploit the already approved drugs and repurpose them therapeutically. We have attempted to screen selected molecules with an affinity towards multiple protein targets in COVID-19 using the Schrödinger suit for in silico predictions. The proteins selected were angiotensin-converting enzyme-2 (ACE2), main protease (MPro), and spike protein. The molecular docking, prime MM-GBSA, induced-fit docking (IFD), and molecular dynamics (MD) simulations were used to identify the most suitable molecule that forms a stable interaction with the selected viral proteins. The ligand-binding stability for the proteins PDB-IDs 1ZV8 (spike protein), 5R82 (Mpro), and 6M1D (ACE2), was in the order of nintedanib > quercetin, nintedanib > darunavir, nintedanib > baricitinib, respectively. The MM-GBSA, IFD, and MD simulation studies imply that the drug nintedanib has the highest binding stability among the shortlisted. Nintedanib, primarily used for idiopathic pulmonary fibrosis, can be considered for repurposing for us against COVID-19.

Design, development and evaluation of Resveratrol transdermal patches for breast cancer therapy.

Resveratrol (RVT) is a polyphenolic phytoestrogen which has shown antiproliferative activity in breast cancer. However, its low bioavailability and short half-life have restricted its use. The current study aimed to develop transdermal patches of RVT and evaluate its site-specific delivery for breast cancer therapy. Different penetration enhancers were screened using a computational tool, quantitative structure propery relationship (QSPR). The best permeation of RVT was observed in a patch comprising hydroxypropyl methylcellulose (HPMC) E15LV: HPMC-K4M: polyvinyl pyrrolidone (PVP) K30 in the ratio of 3:1:2 as release controlling polymers with Glycerol:Capryol 90 (4:1) as penetration enhancer and plasticizer. To assess the localized delivery of RVT, the patch was applied to the breast of female rats. Higher breast tissue disposition with lower systemic concentration was observed compared to oral administration, demonstrated by increased AUC and MRT. Further, the optimized RVT patches were tested in 7,12-Dimethylbenz[a]anthracene (DMBA) induced rat mammary cancer. Compared to oral RVT, the application of RVT tansdermal patches significantly reduced the tumor volume and serum CA 15-3, a cancer biomarker. Thus, the RVT transdermal patch may be a viable approach for ensuring high local concentration of drug for site-specific delivery in breast cancer therapy.

Drug Release and Cytotoxicity of Hyaluronic Acid and Zinc Oxide Gels, An In-Vitro Study.

Hyaluronic acid (HA) is a naturally occurring biopolymer, with a remarkable wound healing property. Zinc-oxide non-eugenol is a material widely used for periodontal dressing in dentistry. However, it has been reported that zinc oxide non-eugenol is toxic to osteoblasts and fibroblasts. Hence, the present study aimed to evaluate the drug release and cytotoxicity of HA and zinc-oxide gels. Hydrogels of HA and zinc oxide were formulated with carbopol as a carrier. In vitro drug release was performed by UV spectrophotometry, dialysis, and vial bag methods. Cytotoxicity assessment of HA and zinc-oxide gels was performed in human periodontal ligament fibroblasts (HPdLF) and human gingival fibroblasts (hGFs). An inverted phase-contrast microscope was used to assess the morphological changes. At 24 and 48 hr, HPdLF cells showed the highest viability in 0.1% low molecular weight-HA (LMW-HA) with a median value of 131.9, and hGFs showed the highest viability in 5% LMW-HA with a median of 129.56. The highest viability of HPdLF cells was observed in 5% high molecular weight-HA (HMW-HA), with a median value of 127.11. hGFs showed the highest viability in 1% HMW-HA with a median value of 97.99. Within the limitations of the present study, we concluded that LMW-HA is more efficient than HMW-HA. Both HPdLF and hGF cells showed complete cell morbidity with zinc-oxide hydrogels. Therefore, zinc oxide-based gels in concentrations as low as 9% could be toxic intraorally to soft tissues that harbor gingival and periodontal ligament fibroblasts.

Transpapillary iontophoretic delivery of resveratrol loaded transfersomes for localized delivery to breast cancer.

Localized drug delivery to the breast tissues is an area of interest as a potential route to ensure site-specific drug delivery. Transpapillary delivery via the mammary papilla has advantages as most breast tumors arise from the milk ducts. The present study explored the plausibility of transpapillary delivery of a phytochemical, resveratrol (RVT), for breast cancer treatment. RVT was encapsulated within the transfersomes (RVT-TRF) to enable a sustained release of the drug using the biomaterial soya phosphatidylcholine (SPC). Iontophoresis was applied to further accelerate the penetration of the RVT-TRF across the mammary papilla to the breast tissue. The RVT-TRF development was optimized by the Design of Experiments (DoE) approach. The in vitro transpapillary iontophoresis study on porcine mammary papilla showed an enhanced penetration of RVT-TRF when compared to passive diffusion. The transpapillary delivery was further confirmed from the in vitro fluorescent microscopy study using FITC conjugated RVT-TRF. The optimized RVT-TRF delivered via transpapillary route showed a higher Cmax and AUC when compared to pure RVT given orally. A significant reduction in the tumor volume and the serum biomarker CA 15-3, when evaluated in a chemically induced breast cancer rat model, provided evidence of the effectiveness of the developed formulation when delivered locally via transpapillary route compared to the oral route. Thus the developed RVT-TRF administered via transpapillary iontophoresis technique is a promising strategy enabling a localized delivery for effective breast cancer therapy.

Understanding the Effect of Functionalization on Loading Capacity and Release of Drug from Mesoporous Silica Nanoparticles: A Computationally Driven Study.

MCM-41, a type of mesoporous silica nanoparticle, has garnered widespread interests as a useful carrier for drug delivery wherein the drug gets adsorbed into the pores of the carrier. To understand the adsorption mechanism and release of the drug at the molecular level, in the current study, it was attempted to generate a computational model for the loading of 5-fluorouracil (5-FU), a chemotherapeutic agent into surface-modified MCM-41. The molecular surface models of the mesoporous silica (MCM-41) nanoparticle with different surface substitutions were created. In the first stage, molecular mechanics (MM) simulations were carried out to obtain the optimized surface structures. Subsequently, a 5-FU drug molecule in its different forms was docked on top of different MCM-41 surfaces to understand the adsorption orientation and energetics. To further validate the results, more accurate quantum mechanical (QM) calculations were also carried out, and the energetics between the QM and MM calculations are found to be similar. All the substitutions (-NH2, -CN, -COOH) except the methyl substitution exhibited favorable interactions compared to the unsubstituted MCM-41 surface which was in accordance with the experimental observations. The release rate of 5-FU from MCM-41 and aminopropyl-substituted MCM-41 (MCM-NH2) was studied using molecular dynamics simulations which revealed that the release rate of 5-FU from the MCM-NH2 surface was slower compared to that of plain MCM-41. The detailed surface characteristics and the adsorption energies from the molecular simulations correlating the loading capacity and release are reported in here.

Recent Updates on Nanocosmeceutical Skin Care and Anti-Aging Products.

Nanotechnology is an innovative area of science that deals with things smaller than 100 nanometers. The influence of nanotechnology in the cosmetic industry is overwhelming since it can enhance the properties attained by the particles at the nano level, including color, solubility, etc, and can also promote the bioavailability of API. A plethora of nanomaterials can be employed in cosmetics, including organic and inorganic nanoparticles. Unlike orthodox carriers, they facilitate easy penetration of the product into the skin, thereby increasing the stability and allowing a controlled drug release so that they can permeate deeper into the skin and start revitalizing it. Nanomaterials rejuvenate the skin by forming an occlusive barrier to inhibit the loss of water from the skin's surface and thereby moisturize the skin. Nano-cosmeceuticals are used to provide better protection against UV radiation, facilitate deeper skin penetration, and give long-lasting effects. Although they still have some safety concerns, hence detailed characterization or risk assessments are required to fulfill the standard safety requirements. In this review, an attempt is made to make a brief overview of various nanocosmeceuticals skincare and anti-aging products.

Molecular dynamics and structure-based virtual screening and identification of natural compounds as Wnt signaling modulators: possible therapeutics for Alzheimer's disease.

Wnt signaling pathway is an evolutionarily conserved pathway responsible for neurogenesis, axon outgrowth, neuronal polarity, synapse formation, and maintenance. Downregulation of Wnt signaling has been found in patients with Alzheimer's disease (AD). Several experimental approaches to activate Wnt signaling pathway have proven to be beneficial in alleviating AD, which is one of the new therapeutic approaches for AD. The current study focuses on the computational structure-based virtual screening followed by the identification of potential phytomolecules targeting different markers of Wnt signaling like WIF1, DKK1, LRP6, GSK-3ß, and acetylcholine esterase. Initially, screening of 1924 compounds from the plant-based library of Zinc database was done for the selected five proteins using docking approach followed by MM-GBSA calculations. The top five hit molecules were identified for each protein. Based on docking score, and binding interactions, the top two hit molecules for each protein were selected as promising molecules for the molecular dynamic (MD) simulation study with the five proteins. Therefore, from this in silico based study, we report that Mangiferin could be a potential molecule targeting Wnt signaling pathway modulating the LRP6 activity, Baicalin for AChE activity, Chebulic acid for DKK1, ZINC103539689 for WIF1, and Morin for GSk-3ß protein. However, further validation of the activity is warranted based on in vivo and in vitro experiments for better understanding and strong claim. This study provides an in silico approach for the identification of modulators of the Wnt signaling pathway as a new therapeutic approach for AD.

Structure-based docking, pharmacokinetic evaluation, and molecular dynamics-guided evaluation of traditional formulation against SARS-CoV-2 spike protein receptor bind domain and ACE2 receptor complex.

There is an urgent need for reliable cure and preventive measures in this hour of the outbreak of SARS-CoV-2. Siddha- and Ayurvedic-based classical formulations have antiviral properties and great potential therapeutic choice in this pandemic situation. In the current study, in silico-based analysis for the binding potential of phytoconstituents from the classical formulations suggested by the Ministry of Ayush (Kabasura Kudineer, Shwas Kuthar Rasa with Kantakari and pippali churna, Talisadi churna) to the interface domain of the SARS-CoV-2 receptor-binding domain and angiotensin-converting enzyme 2 was performed. Maestro software from Schrodinger and tools like Glide Docking, induced fit docking, MM-GBSA, molecular dynamics (MD) simulation, and thermal MM-GBSA was used to analyze the binding of protein PDB ID:6VW1 and the selected 133 ligands in comparison with drug molecules like favipiravir and ribavirin. QikProp-based ADMET evaluation of all the phytoconstituents found them nontoxic and with drug-like properties. Selection of top ten ligands was made based on docking score for further MM-GBSA analysis. After performing IFD of top five molecules iso-chlorogenic acid, taxiphyllin, vasicine, catechin and caffeic acid, MD simulation and thermal MM-GBSA were done. Iso-chlorogenic acid had formed more stable interaction with key residue among all phytoconstituents. Computational-based study has highlighted the potential of the many constituents of traditional medicine to interact with the SARS-CoV-2 RBD and ACE2, which might stop the viral entry into the cell. However, in vivo experiments and clinical trials are necessary for supporting this claim. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01917-z.