Phenylacetaldehyde induced olfactory conditioning in Drosophila melanogaster (Diptera: Drosophilidae) larvae.

Phenylacetaldehyde (PAH), an aromatic odorant, exists in varied fruits including overripe bananas and prickly pear cactus, the 2 major host fruits of Drosophila melanogaster. It acts as a potent ligand for the Ionotropic receptor 84a (IR84a) and the Odorant receptor 67a (OR67a), serving as an important food and courtship cue for adult fruit flies. Drosophila melanogaster larvae respond robustly to diverse feeding odorants, such as ethyl acetate (EA), an aliphatic ester. Since the chemical identity and concentration of an odorant are vital neural information handled by the olfactory system, we studied how larvae respond to PAH, an aromatic food odorant with aphrodisiac properties for adult flies. Our findings revealed that PAH attracted larvae significantly in a dose-dependent manner. Larvae could also be trained with PAH associated to appetitive and aversive reinforcers. Thus, like EA, PAH might serve as an important odorant cue for larvae, aiding in food tracking and survival in the wild. Since IR84a/IR8a complex primarily governs PAH response in adult flies, we examined expression of Ir84a and Ir8a in early third-instar larvae. Our experiments showed the presence of Ir8a, a novel finding. However, contrary to adult flies, PAH-responsive Ir84a was not found. Our behavioral experiments with Ir8a1 mutant larvae exhibited normal chemotaxis to PAH, whereas Orco1 mutant showed markedly reduced chemotaxis, indicating an OR-mediated neural circuitry for sensing of PAH in larvae. The results obtained through this study are significantly important as information on how larvae perceive and process PAH odorant at the neuronal level is lacking.

Galectins-Potential Therapeutic Targets for Neurodegenerative Disorders.

Advancements in medicine have increased the longevity of humans, resulting in a higher incidence of chronic diseases. Due to the rise in the elderly population, age-dependent neurodegenerative disorders are becoming increasingly prevalent. The available treatment options only provide symptomatic relief and do not cure the underlying cause of the disease. Therefore, it has become imperative to discover new markers and therapies to modulate the course of disease progression and develop better treatment options for the affected individuals. Growing evidence indicates that neuroinflammation is a common factor and one of the main inducers of neuronal damage and degeneration. Galectins (Gals) are a class of ß-galactoside-binding proteins (lectins) ubiquitously expressed in almost all vital organs. Gals modulate various cellular responses and regulate significant biological functions, including immune response, proliferation, differentiation, migration, and cell growth, through their interaction with glycoproteins and glycolipids. In recent years, extensive research has been conducted on the Gal superfamily, with Gal-1, Gal-3, and Gal-9 in prime focus. Their roles have been described in modulating neuroinflammation and neurodegenerative processes. In this review, we discuss the role of Gals in the causation and progression of neurodegenerative disorders. We describe the role of Gals in microglia and astrocyte modulation, along with their pro- and anti-inflammatory functions. In addition, we discuss the potential use of Gals as a novel therapeutic target for neuroinflammation and restoring tissue damage in neurodegenerative diseases.

Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease.

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.

A Saffron based Polyherbal Formulation DuK Prevents Hepatocellular Carcinoma in Male Wistar Rats.

BACKGROUND: Duk is a well-established traditional drug which has been used since time immemorial by Indian practitioners to cure various human ailments. OBJECTIVE: The purpose of this study was to explore the anti-cancer activity and the possible mechanism of Duk against diethylnitrosamine (DEN)-initiated hepatocarcinogenesis. METHODS & RESULTS: We administered Duk at 3 doses, viz., 75, 150, and 300 mg/kg/day, 2 weeks before the DEN and continued it for 16 weeks. After 1 week of DEN recovery, 2-aminoacetylflourine (2-AAF) was administered to promote hepatocarcinogenesis. We found that Duk significantly reduced the DEN and 2-AAF induced phenotypical changes in rats and restored the activities of serum markers. Furthermore, Duk counteracted the oxidative stress induced by carcinogens as observed by restoration in the levels of superoxide dismutase (SOD) and catalase (CAT). Duk significantly diminished the levels of malondialdehyde (MDA) in a dose dependent manner and restored the liver microarchitecture as assessed by histopathological studies. The results of immunohistochemical staining showed that Duk inhibited the DEN-induced decrease in the number of cells positive for Bid and Caspase-9. It also reduces the number of cells positive for Cyclin D. CONCLUSION: Duk significantly protects rat liver from hepatocarcinogenesis by regulating oxidative damage and restoring serum markers. The chemopreventive effect of Duk might be through induction of apoptosis.

Acute Exposure to Arsenic Affects Pupal Development and Neurological Functions in Drosophila melanogaster.

Millions of people in developing countries are affected by arsenic (As) toxicity and its prevalence. Arsenic's detrimental effects on humans have been amplified by an unacceptable level of exposure to food and drinking water, the ongoing rise in industrial usage, and several other occupational conditions. Due to increased cellular absorption and the ability to cross the blood-brain barrier (BBB), inorganic arsenic (iAs) is extremely hazardous to living organisms in its trivalent form. Arsenic toxicity damages an organism's tissues and organs, resulting in skin cancer, circulatory system abnormalities, and central nervous system disorders. However, a competent model system is required to investigate the acute effects of arsenic on the brain, cognition ability, and to assess any behavioral impairment. Hence, Drosophila, with its short generation time, genomic similarities with humans, and its availability for robust behavioral paradigms, may be considered an ideal model for studying arsenic toxicity. The present study helps to understand the toxic effects of acute arsenic treatment on the behavior, cognition, and development of Drosophila in a time-dependent manner. We found that the exposure of fruit flies to arsenic significantly affected their locomotor abilities, pupae size, cognitive functions, and neurobehavioral impairment. Hence, providing a better understanding of how arsenic toxicity affects the brain leading to acute behavioral disorders and neurological alterations, this study will lead to a better understanding of the mechanisms.

Inhibition of microtubule affinity regulating kinase 4 by an acetylcholinesterase inhibitor, Huperzine A: Computational and experimental approaches.

Microtubule affinity regulating kinase 4 (MARK4), 752 amino acids long, belonging to the AMPK superfamily, plays a vital role in regulating microtubules due to its potential to phosphorylate microtubule-associated proteins (MAP's) and thus, MARK4 plays a key role in Alzheimer's disease (AD) pathology. MARK4 is a druggable target for cancer, neurodegenerative diseases, and metabolic disorders. In this study, we have evaluated the MARK4 inhibitory potential of Huperzine A (HpA), an acetylcholinesterase inhibitor (AChEI), a potential AD drug. Molecular docking revealed the key residues governing the MARK4-HpA complex formation. The structural stability and conformational dynamics of the MARK4-HpA complex was assessed by employing Molecular dynamics (MD) simulation. The results suggested that the binding of HpA with MARK4 leads to minimal structural alterations in the native conformation of MARK4, implying the stability of the MARK4-HpA complex. Isothermal titration calorimetry (ITC) studies deciphered that HpA binds to MARK4 spontaneously. Moreover, the kinase assay depicted significant inhibition of MARK by HpA (IC50 = 4.91 µM), implying it to be a potent MARK4 inhibitor that can be implicated in the treatment of MARK4-directed diseases.

Role of lisinopril in the therapeutic management of cardiovascular disease by targeting microtubule affinity regulating kinase 4: molecular docking and molecular dynamics simulation approaches.

Cardiovascular diseases (CVDs) are a major cause of premature adult death. Various factors contribute to the development of CVDs, such as atherosclerosis leading to myocardial infarction (MI), and compromised cardiac function after MI leads to chronic heart failure with systemic health complications and a high mortality rate. Microtubule detyrosination has rapidly evolved as an essential mechanism to regulate cardiomyocyte contractility. Microtubule affinity regulating kinase 4 (MARK4) regulates cardiomyocyte contractility in a way that it promotes phosphorylation of microtubule-associated protein 4, thereby facilitating the access of vasohibin 2-a tubulin carboxypeptidase-to microtubules for the detyrosination of α-tubulin. Lisinopril, a drug belonging to the class of angiotensin-converting enzyme inhibitors, is used to treat high blood pressure. This is also used to treat heart failure, which plays a vital role in improving the survival rate post-heart attack. In this study, we will evaluate the MARK4 inhibitory potential of lisinopril employing molecular docking and molecular dynamics (MD) simulation approaches. Molecular docking analysis suggested that lisinopril binds to MARK4 with a significant binding affinity forming interactions with functionally essential residues of MARK4. Additionally, MD simulation deciphered the structural dynamics and stability of the MARK4-lisinopril complex. The findings of MD studies established that minimal structural deviations are observed during simulation, affirming the stability of the MARK4-lisinopril complex. Altogether, this study demonstrates lisinopril's crucial role in the therapeutic management of CVD by targeting MARK4.Communicated by Ramaswamy H. Sarma.

Drosophila melanogaster Chemosensory Pathways as Potential Targets to Curb the Insect Menace.

From a unicellular bacterium to a more complex human, smell and taste form an integral part of the basic sensory system. In fruit flies Drosophila melanogaster, the behavioral responses to odorants and tastants are simple, though quite sensitive, and robust. They explain the organization and elementary functioning of the chemosensory system. Molecular and functional analyses of the receptors and other critical molecules involved in olfaction and gustation are not yet completely understood. Hence, a better understanding of chemosensory cue-dependent fruit flies, playing a major role in deciphering the host-seeking behavior of pathogen transmitting insect vectors (mosquitoes, sandflies, ticks) and crop pests (Drosophila suzukii, Queensland fruit fly), is needed. Using D. melanogaster as a model organism, the knowledge gained may be implemented to design new means of controlling insects as well as in analyzing current batches of insect and pest repellents. In this review, the complete mechanisms of olfactory and gustatory perception, along with their implementation in controlling the global threat of disease-transmitting insect vectors and crop-damaging pests, are explained in fruit flies.

Emerging therapeutic developments in neurodegenerative diseases: A clinical investigation.

Despite a century of intensive research, there is still a lack of disease-modifying treatments for neurodegenerative diseases that pose a threat to human society. A well-documented knowledge and resource gap has impeded the translation of fundamental research into promising therapies. In addition, the analysis of extensive preclinical data to allow the improved selection of therapeutic technologies and clinical candidates for further development is challenging. To address this need, we describe technologies that have emerged over the past decade that have enabled the development of novel, high-quality, cost-effective treatments for major neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Moreover, we benchmark emerging technologies that have been adopted by top pharmaceutical companies looking to bridge the gap between drug discovery and drug development in neurodegenerative disease.

DeePred-BBB: A Blood Brain Barrier Permeability Prediction Model With Improved Accuracy.

The blood-brain barrier (BBB) is a selective and semipermeable boundary that maintains homeostasis inside the central nervous system (CNS). The BBB permeability of compounds is an important consideration during CNS-acting drug development and is difficult to formulate in a succinct manner. Clinical experiments are the most accurate method of measuring BBB permeability. However, they are time taking and labor-intensive. Therefore, numerous efforts have been made to predict the BBB permeability of compounds using computational methods. However, the accuracy of BBB permeability prediction models has always been an issue. To improve the accuracy of the BBB permeability prediction, we applied deep learning and machine learning algorithms to a dataset of 3,605 diverse compounds. Each compound was encoded with 1,917 features containing 1,444 physicochemical (1D and 2D) properties, 166 molecular access system fingerprints (MACCS), and 307 substructure fingerprints. The prediction performance metrics of the developed models were compared and analyzed. The prediction accuracy of the deep neural network (DNN), one-dimensional convolutional neural network, and convolutional neural network by transfer learning was found to be 98.07, 97.44, and 97.61%, respectively. The best performing DNN-based model was selected for the development of the "DeePred-BBB" model, which can predict the BBB permeability of compounds using their simplified molecular input line entry system (SMILES) notations. It could be useful in the screening of compounds based on their BBB permeability at the preliminary stages of drug development. The DeePred-BBB is made available at https://github.com/12rajnish/DeePred-BBB.

Epigallocatechin 3-gallate: From green tea to cancer therapeutics.

Epigallocatechin 3-gallate (EGCG) possesses various biological functions, including anti-cancer and anti-inflammatory properties. EGCG is an abundant polyphenolic component originating from green tea extract that has exhibited versatile bioactivities in combating several cancers. This review highlights the pharmacological features of EGCG and its therapeutic implications in cancer and other metabolic diseases. It modulates numerous signaling pathways, regulating cells' undesired survival and proliferation, thus imparting strong tumor chemopreventive and therapeutic effects. EGCG initiates cell death through the intrinsic pathway and causes inhibition of EGFR, STAT3, and ERK pathways in several cancers. EGCG alters and inhibits ERK1/2, NF-κB, and Akt-mediated signaling, altering the Bcl-2 family proteins ratio and activating caspases in tumor cells. This review focuses on anti-cancer, anti-oxidant, anti-inflammatory, anti-angiogenesis, and apoptotic effects of EGCG. We further highlighted the potential of EGCG in different types of cancer, emphasizing clinical trials formulations that further improve our understanding of the therapeutic management of cancer and inflammatory diseases.

Structural and bioactive characteristics of a dextran produced by Lactobacillus kunkeei AK1.

In this study, structural and techno-functional characteristics of an exopolysaccharide (EPS) produced by Lactobacillus kunkeei AK1 were determined. High-performance liquid chromatography (HPLC) analysis demonstrated that EPS AK1 was composed of only glucose units. 1H and 13C Nuclear magnetic resonance (NMR) analysis revealed that EPS AK1 was a dextran type EPS containing 4.78% (1 â†’ 4)-linked α-d-glucose branches. The molecular weight of EPS AK1 was determined to be 45 kDa by Gel Permeation Chromatography (GPC) analysis. A high level of thermal stability up to 280 °C was determined for dextran AK1 detected by Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA). Dextran AK1 appeared as regular spheres with compact morphology and as irregular particles in the solution with no clear cross-linking between the chains of the polysaccharide observed by Scanning electron microscopy (SEM) and Atomic force microscopy (AFM) analysis, respectively. X-ray diffraction analysis (XRD) analysis demonstrated that dextran AK1 had a crystalline structure. A relatively strong antioxidant activity was observed for dextran AK1 determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging and cupric reducing antioxidant capacity (CUPRAC) tests. Finally, only a digestion ratio of 3.1% was observed for dextran AK1 following the in vitro simulated gastric digestion test.

Tailored construction of one-dimensional TiO2/Au nanofibers: Validation of an analytical assay for detection of diphenylamine in food samples.

We report a one-dimensional titanium dioxide encapsulated with gold heterojunction nanofibers (TiO2/Au NFs) as robust electrocatalysts for electrochemical detection of diphenylamine (DPA). A TiO2/Au NFs were successfully synthesized by a coaxial electrospinning method. The formation of TiO2/Au NFs was confirmed by various analytical and spectroscopic approaches. The fabricated TiO2/Au NFs modified screen-printed carbon electrodes (SPCE) exhibit a well-enhanced detection activity towards DPA sensing as compared to other electrodes. Under the experimental conditions, the proposed electrode leading to the sensing range from 0.05 to 60 µM with a detection limit of 0.009 µM was obtained for the DPA detection. Moreover, the TiO2/Au NFs/SPCE showed good selectivity towards the electrochemical oxidation of DPA. Interestingly, the TiO2/Au NFs modified electrode was then applied to detect the effect of DPA on spiked content in the food samples.

Bioactive phytoconstituents as potent inhibitors of casein kinase-2: dual implications in cancer and COVID-19 therapeutics.

Casein kinase 2 (CK2) is a conserved serine/threonine-protein kinase involved in hematopoietic cell survival, cell cycle control, DNA repair, and other cellular processes. It plays a significant role in cancer progression and viral infection. CK2 is considered a potential drug target in cancers and COVID-19 therapy. In this study, we have performed a virtual screening of phytoconstituents from the IMPPAT database to identify some potential inhibitors of CK2. The initial filter was the physicochemical properties of the molecules following the Lipinski rule of five. Then binding affinity calculation, PAINS filter, ADMET, and PASS analyses followed by interaction analysis were carried out to discover nontoxic and better hits. Finally, two compounds, stylopine and dehydroevodiamines with appreciable affinity and specific interaction towards CK2, were identified. Their time-evolution analyses were carried out using all-atom molecular dynamics simulation, principal component analysis and free energy landscape. Altogether, we propose that stylopine and dehydroevodiamines can be further explored in in vitro and in vivo settings to develop anticancer and antiviral therapeutics.

Effects of associated bacteria on the pathogenicity and reproduction of the insect-parasitic nematode Rhabditis blumi (Nematoda: Rhabditida).

Three bacteria, Alcaligenes faecalis , Flavobacterium sp., and Providencia vermicola , were isolated from dauer juveniles of Rhabditis blumi . The pathogenic effects of the bacteria against 4th instar larvae of Galleria mellonella were investigated. Providencia vermicola and Flavobacterium sp. showed 100% mortality at 48 h after haemocoelic injection, whereas A. faecalis showed less than 30% mortality. Dauer juveniles showed 100% mortality against G. mellonella larvae, whereas axenic juveniles, which do not harbor associated bacteria, exhibited little mortality. All of the associated bacteria were used as a food source for nematode growth, and nematode yield differed with bacterial species. Among the bacterial species, P. vermicola was most valued for nematode yield, showing the highest yield of 5.2 × 10(4) nematodes/mL in the plate. In bacterial cocultures using two of the three associated bacteria, one kind stimulated the other. The highest total bacterial yield of 12.6 g/L was obtained when the inoculum ratio of P. vermicola to A. faecalis was 10:1. In air-lift bioreactors, the nematode growth rate increased with an increasing level of dissolved oxygen. The maximum nematode yield of 1.75 × 10(5) nematodes/mL was obtained at 192 h with an aeration rate of 6 vvm.

New Horizons in the Treatment of Neurological Disorders with Tailorable Gold Nanoparticles.

Neurological disorders, such as epilepsy, dementia, Parkinson's disease and Alzheimer's disease, occur due to disorganization of the neurons in the nervous system. Disturbances in the nervous system cause problems with the memory, senses and moods. In order to treat such disorders, scientists have been working extensively, utilizing different approaches. Nanoneurotechnology has emerged as a promising tool to manage these complicated disorders, where nanoparticles with their tunable properties such as size, shape, increased solubility, biodegradability, surface area and sharp penetration through the biological barriers, target the central nervous system. This technology targets damaged neurons without affecting healthy neurons and the Blood-Brain Barrier (BBB). In this review, we discuss neurological disorders and challenges in their diagnosis and treatment by emphasizing on the role of tailorable gold nanoparticles in therapeutic drug approaches.

Construction of strontium phosphate/graphitic-carbon nitride: A flexible and disposable strip for acetaminophen detection.

A facile technique has been used to synthesize the strontium phosphate interlinked with graphitic carbon nitride nanosheets (SrP/g-CN NSs) nanocomposite for highly selective detection of acetaminophen (AP). The formation of SrP/g-CN NSs nanocomposite is evidenced by several spectroscopic and analytical methods. It was demonstrated that the SrP/g-CN NSs modified screen-printed carbon electrode (SPCE) exhibits excellent catalytic performance with low peak potential towards AP detection than those of pristine SrP-, g-CN NSs-, and bare- SPCEs. The outstanding electrochemical performance can be attributed to the robust synergistic effect between SrP and g-CN NSs. Likewise, g-CN NSs possess a porous multilayer network, which provides a large surface area, fast charge transferability, electrical conductivity, and numerous active sites. Under the optimal conditions, the fabricated sensor could detect AP with a linear relationship range from 0.01 to 370 µM, and the detection limit is calculated to be as low as 2.0 nM. The proposed sensor is successfully used to determine AP in water samples with satisfactory results.

Rational Confinement of Yttrium Vanadate within Three-Dimensional Graphene Aerogel: Electrochemical Analysis of Monoamine Neurotransmitter (Dopamine).

Real-time monitoring of neurotransmitter levels is of tremendous technological demand, which requires more sensitive and selective sensors over a dynamic concentration range. As a use case, we report yttrium vanadate within three-dimensional graphene aerogel (YVO/GA) as a novel electrocatalyst for detecting dopamine (DA). This synergy effect endows YVO/GA nanocomposite with good electrochemical behaviors for DA detection compared to other electrodes. Benefiting from tailorable properties, it provides a large specific surface area, rapid electron transfer, more active sites, good catalytic activity, synergic effect, and high conductivity. The essential analytical parameters were estimated from the calibration plot, such as a limit of detection (1.5 nM) and sensitivity (7.1 µA µM-1 cm-2) with the YVO/GA sensor probe electrochemical approach. The calibration curve was fitted with the correlation coefficient of 0.994 in the DA concentration range from 0.009 to 83 µM, which is denoted as the linear working range. We further demonstrate the proposed YVO/GA sensor's applicability to detect DA in human serum sample with an acceptable recovery range. Our results imply that the developed sensor could be applied to the early analysis of dementia, psychiatric, and neurodegenerative disorders.

Enhanced Photocatalytic Activity of Cu2O Cabbage/RGO Nanocomposites under Visible Light Irradiation.

Towards the utilization of Cu2O nanomaterial for the degradation of industrial dye pollutants such as methylene blue and methyl orange, the graphene-incorporated Cu2O nanocomposites (GCC) were developed via a precipitation method. Using Hummers method, the grapheme oxide (GO) was initially synthesized. The varying weight percentages (1-4 wt %) of GO was incorporated along with the precipitation of Cu2O catalyst. Various characterization techniques such as Fourier-transform infra-red (FT-IR), X-ray diffraction (XRD), UV-visible diffused reflectance (UV-DRS), Raman spectroscopy, thermo gravimetric analysis (TGA), energy-dispersive X-ray analysis (EDX), and electro chemical impedance (EIS) were followed for characterization. The cabbage-like morphology of the developed Cu2O and its composites were ascertained from field-emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HR-TEM). In addition, the growth mechanism was also proposed. The results infer that 2 wt % GO-incorporated Cu2O composites shows the highest value of degradation efficiency (97.9% and 96.1%) for MB and MO at 160 and 220 min, respectively. Further, its catalytic performance over visible region (red shift) was also enhanced to an appreciable extent, when compared with that of other samples.

Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy.

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of -27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µg/cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.