Drug Polymeric Carrier of Aceclofenac Based on Amphiphilic Chitosan Micelles.

Amphiphilic micelles based on chitosan (CS) were applied as drug carriers of aceclofenac (ACF) as a potential method to induce its bioavailability and therapeutic efficiency. N-octyl-N,O-succinyl CS (OSCS), an amphiphilic CS derivative, was successfully synthesized and loaded physically by ACF at different pH values and using different dosages of ACF, forming ACF-loaded polymeric micelles (PMs). The obtained PMs and ACF-loaded PMs were characterized by different analytical techniques, including AFM, TEM, DLS, UV-vis spectrophotometry, 1H NMR spectroscopy, and FT-IR spectroscopy. The pH 5 sample with a 30% ACF/polymer ratio showed the highest ACF loading capacity (LC) and entrapment efficiency (EE). In vitro release behaviors of pure ACF and ACF-loaded PMs at each release point indicated that the release profile of pH-responsive PMs loaded with ACF demonstrated quicker release rates (94% after 480 min) compared to the release behavior noticed for free ACF (59.56% after 480 min). Furthermore, the release rates exhibit a notable rise when the pH is increased from 1.2 to 4.7. In the carrageenan-induced inflammation model of paw edema in rats, it has been demonstrated that the injection of ACF-loaded PMs (at a dose of 10 mg/kg) resulted in a strengthened inflammatory activity compared to the injection of free ACF at equivalent dosages as well as at time intervals. However, the use of ACF-loaded PMs for a duration of 6 h displayed a notable reduction of paw edema, with an inhibition percentage of 85.09%, in contrast to the 74.9% inhibition percentage observed for the free ACF medication.

Therapeutic potential of natural products in inflammation: underlying molecular mechanisms, clinical outcomes, technological advances, and future perspectives.

Chronic inflammation is a common underlying factor in many major diseases, including heart disease, diabetes, cancer, and autoimmune disorders, and is responsible for up to 60% of all deaths worldwide. Metformin, statins, and corticosteroids, and NSAIDs (non-steroidal anti-inflammatory drugs) are often given as anti-inflammatory pharmaceuticals, however, often have even more debilitating side effects than the illness itself. The natural product-based therapy of inflammation-related diseases has no adverse effects and good beneficial results compared to substitute conventional anti-inflammatory medications. In this review article, we provide a concise overview of present pharmacological treatments, the pathophysiology of inflammation, and the signaling pathways that underlie it. In addition, we focus on the most promising natural products identified as potential anti-inflammatory therapeutic agents. Moreover, preclinical studies and clinical trials evaluating the efficacy of natural products as anti-inflammatory therapeutic agents and their pragmatic applications with promising outcomes are reviewed. In addition, the safety, side effects and technical barriers of natural products are discussed. Furthermore, we also summarized the latest technological advances in the discovery and scientific development of natural products-based medicine.

Intra Nasal Use of Ethylene Diamine Tetra Acetic Acid for Improving Olfactory Dysfunction Post COVID-19.

BACKGROUND: COVID-19 has been associated with olfactory dysfunction in many infected patients. The rise of calcium levels in the nasal secretions plays an essential role in the olfaction process with a desensitization effect on the olfactory receptor neurons and a negative impact on the olfaction transmission. Ethylene diamine tetra acetic acid (EDTA) is a chelating agent that can bind free calcium in the nasal secretions, thereby reducing the adverse effects of calcium on olfactory function. OBJECTIVES: The objective of this work is to demonstrate the effect of intranasal EDTA on improving olfactory dysfunction following COVID-19. METHODS: Fifty patients with a history of COVID-19 and olfactory dysfunction that persisted for more than 6 months were enrolled in the current prospective randomized clinical trial. Participants were randomized into 2 equal groups. Twenty-five patients were treated with olfactory training only, while the remaining 25 patients received treatment with olfactory training and a topical nasal spray of ethylene diamine tetra acetic acid. The olfactory function was assessed before treatment and 3 months later using the Sniffin' Sticks test. Additionally, the determination of calcium level in the nasal secretions was performed using an ion-selective electrode before treatment and 3 months later. RESULTS: Eighty-eight percent of the patients treated with olfactory training in addition to EDTA exhibited clinical improvement, while 60% showed improvement in patients treated with olfactory training only. Furthermore, a significant decrease in the measured calcium level in the nasal secretions was demonstrated after the use of ethylene diamine tetra compared to patients treated with olfactory training only. CONCLUSION: Ethylene diamine tetra acetic acid may be associated with an improvement of the olfactory function post-COVID-19.

Investigating the superiority of chitosan/D-alpha-tocopheryl polyethylene glycol succinate binary coated bilosomes in promoting the cellular uptake and anti-SARS-CoV-2 activity of polyphenolic herbal drug candidate.

The evolution of a safe and effective therapeutic system to conquer SAR-CoV-2 infection deemed to be a crucial worldwide demand. Curcumin (CUR) is a phytomedicinal polyphenolic drug that exhibited a well-reported anti-SAR-CoV-2. However, the therapeutic activity of CUR is hindered by its poor intestinal permeability and diminished aqueous solubility. Therefore, this study strived to develop D-alpha-tocopheryl polyethylene glycol succinate (TPGS) bilosomes (TPGS-Bs) adopting 23 full factorial designs to improve solubility and intestinal permeability of CUR, hence boosting its anti-SARS-CoV-2 activity. Eight experimental runs were attained considering three independent variables: soybean phosphatidylcholine amount (mg) (SPC amount), bile salt amount (mg) (BS amount), and TPGS amount (mg). The optimum formula (F4) exhibited EE % (88.5 ± 2.4 %), PS (181.5 ± 21.6 nm), and ZP (-34.5 ± 3.7 mV) with desirability value = 0.739 was picked as an optimum formula. Furthermore, the optimum formula (F4) was extra coated with chitosan (CS) to improve permeability and anti-SAR-CoV-2 activity. Caco-2 cell uptake after 2 hr revealed the superiority of CS-F4 and F4 by 6 and 5 folds relative to CUR dispersion, respectively. Furthermore, CS-F4 exhibited a significantly higher anti-SARS-CoV-2 activity with IC50 (0.24 µg/ml) by 8.3 times than F4 (1.99 µg/ml). Besides, the mechanistic study demonstrated that the two formulae imparted antiviral activity by inhibiting the spike protein by virucidal potentialities. In addition, the conducted molecular docking and MD simulations towards the SARS-CoV-2 Mpro enzyme confirmed the interaction of CUR with key residues of the virus enzymes. Based on the preceded, CS-F4 could be assumed to be used to effectively eradicate SARS-CoV-2 infection.

Gypsogenin Battling for a Front Position in the Pentacyclic Triterpenes Game of Thrones on Anti-Cancer Therapy: A Critical Review-Dedicated to the Memory of Professor Hanaa M. Rady.

In the last decade, gypsogenin has attracted widespread attention from medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin has proved itself as a new anti-proliferative player battling for a frontline position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present the most important reactions of gypsogenin via modification of its four functional groups. Furthermore, we demonstrate insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospective rational design. The present article opens a new venue for a better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

The Potential Roles of Ficus carica Extract in the Management of COVID-19 Viral Infections: A Computer-Aided Drug Design Study.

INTRODUCTION: The conventional processes of drug discovery are too expensive, time-consuming and the success rate is limited. Searching for alternatives that have evident safety and potential efficacy could save money, time and improve the current therapeutic regimen outcomes. METHOD: Clinical phytotherapy implies the use of extracts of natural origin for prophylaxis, treatment, or management of human disorders. In this work, the potential role of common Fig (Ficus carica) in the management of COVID-19 infections has been explored. The antiviral effects of Cyanidin-3-rhamnoglucoside which is abundant in common Figs have been illustrated on COVID-19 targets. The immunomodulatory effect and the ability to ameliorate the cytokine storm associated with coronavirus infections have also been highlighted. This work involves various computational studies to investigate the potential roles of common figs in the management of COVID-19 viral infections. RESULTS: Two molecular docking studies of all active ingredients in common Figs were conducted starting with MOE to provide initial insights, followed by Autodock Vina for further confirmation of the results of the top five compounds with the best docking score. CONCLUSION: Finally, Molecular dynamic simulation alongside MMPBSA calculations were conducted using GROMACS to endorse and validate the entire work.

Intranasal inorganic cerium oxide nanoparticles ameliorate oxidative stress induced motor manifestations in haloperidol-induced parkinsonism.

Cerium oxide nanoparticles (CONPs), owing to their radical scavenging property, have recently emerged as a therapeutic candidate for oxidative stress-mediated neurological diseases. However, oral and intravenous administration of CONPs is limited due to their poor physicochemical characteristics, low bioavailability, rapid systemic clearance, poor blood-brain penetration and dose-dependent toxicity. To overcome these challenges, we developed intranasal CONPs and evaluated their potential in the experimental PD model. CONPs were prepared by homogenous precipitation using tween 80 as a stabilizer and methanol/water as solvent. The optimization was done using Central Composite Design (CCD). The CONPs synthesis was confirmed by UV and FTIR. The optimized CONPs were small-sized (105.1 ± 5.78 nm), spherical (TEM), uniform (PDI, 0.119 ± 0.006) and stable (ZP, -22.7 ± 1.02 mV). Energy-dispersive X-ray analysis showed characteristic signals of Ce in developed CONPs. The X-ray diffraction pattern described the cubic fluorite structure and nano-crystalline nature of CONPs. The CONP anti-oxidant activity was found to be 93.60 ± 0.32% at 25 µg/mL concentration. Finally, motor manifestation studies like the forced swim test, locomotor test, akinesia, catalepsy, and muscle coordination test were conducted to assess the motor dysfunctions and behavioral activity in all four animal groups. Results of the in vivo motor manifestation studies in the haloperidol-induced PD rat model showed that co-administration of intranasal CONPs along with a half dose of levodopa resulted in significant protection, and results were significantly different from the untreated group but not significantly different from the healthy group. In conclusion, intranasal CONPs can be useful in ameliorating oxidative stress through their antioxidant effect and could be prospective therapeutics for the treatment of motor manifestations in Parkinson's disease.

Extraction, characterization of polyphenols from certain medicinal plants and evaluation of their antioxidant, antitumor, antidiabetic, antimicrobial properties, and potential use in human nutrition.

Introduction: Dietary medicinal plants are among the most sought-after topics in alternative medicine today due to their preventive and healing properties against many diseases. Aim: This study aimed to extract and determine the polyphenols from indigenous plants extracts, i.e., Mentha longifolia, M. arvensis, Tinospora cordifolia, Cymbopogon citratus, Foeniculum vulgare, Cassia absus, Camellia sinensis, Trachyspermum ammi, C. sinensis and M. arvensis, then evaluate the antioxidant, cytotoxicity, and antimicrobial properties, besides enzyme inhibition of isolated polyphenols. Methods: The antioxidant activity was evaluated by DPPH, Superoxide radical, Hydroxyl radical (OH.), and Nitric oxide (NO.) scavenging activity; the antidiabetic activity was evaluated by enzymatic methods, and anticancer activity using MTT assay, while the antibacterial activity. Results: The results showed that tested medicinal plants' polyphenolic extracts (MPPE) exhibited the most significant antioxidant activity in DPPH, hydroxyl, nitric oxide, and superoxide radical scavenging methods because of the considerable amounts of total polyphenol and flavonoid contents. UHPLC profile showed twenty-five polyphenol complexes in eight medicinal plant extracts, categorized into phenolic acids, flavonoids, and alkaloids. The main polyphenol was 3-Feroylquinic acid (1,302 mg/L), also found in M. longifolia, C. absus, and C. sinensis, has a higher phenolic content, i.e., rosmarinic acid, vanillic acid, chlorogenic acid, p-coumaric acid, ferulic acid, gallic acid, catechin, luteolin, 7-O-neohesperideside, quercetin 3,7-O-glucoside, hesperidin, rutin, quercetin, and caffeine in the range of (560-780 mg/L). At the same time, other compounds are of medium content (99-312 mg/L). The phenolics in C. sinensis were 20-116% more abundant than those in M. longifolia, C. absus, and other medicinal plants. While T. cordifolia is rich in alkaloids, T. ammi has a lower content. The MTT assay against Caco-2 cells showed that polyphenolic extracts of T. ammi and C. citratus had maximum cytotoxicity. While M. arvensis, C. sinensis, and F. vulgare extracts showed significant enzyme inhibition activity, C. sinensis showed minor inhibition activity against α-amylase. Furthermore, F. vulgare and C. sinensis polyphenolic extracts showed considerable antibacterial activity against S. aureus, B. cereus, E. coli, and S. enterica. Discussion: The principal component analysis demonstrated clear separation among medicinal plants' extracts based on their functional properties. These findings prove the therapeutic effectiveness of indigenous plants and highlight their importance as natural reserves of phytogenic compounds with untapped potential that needs to be discovered through advanced analytical methods.

Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis.

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.

Critical Analysis and Optimization of Stoichiometric Ratio of Drug-Coformer on Cocrystal Design: Molecular Docking, In Vitro and In Vivo Assessment.

In this present research, an attempt has been made to address the influence of drug-coformer stoichiometric ratio on cocrystal design and its impact on improvement of solubility and dissolution, as well as bioavailability of poorly soluble telmisartan. The chemistry behind cocrystallization and the optimization of drug-coformer molar ratio were explored by the molecular docking approach, and theoretical were implemented practically to solve the solubility as well as bioavailability related issues of telmisartan. A new multicomponent solid form, i.e., cocrystal, was fabricated using different molar ratios of telmisartan and maleic acid, and characterized by SEM, DSC and XRD studies. The molecular docking study suggested that specific molar ratios of drug-coformer can successfully cluster with each other and form a specific geometry with favourable energy conformation to form cocrystals. Synthesized telmisartan-maleic acid cocrystals showed remarkable improvement in solubility and dissolution of telmisartan by 9.08-fold and 3.11-fold, respectively. A SEM study revealed the formation of cocrystals of telmisartan when treated with maleic acid. DSC and XRD studies also confirmed the conversion of crystalline telmisartan into its cocrystal state upon treating with maleic acid. Preclinical investigation revealed significant improvement in the efficacy of optimized cocrystals in terms of plasma drug concentration, indicating enhanced bioavailability through improved solubility as well as dissolution of telmisartan cocrystals. The present research concluded that molecular docking is an important path in selecting an appropriate stoichiometric ratio of telmisartan: maleic acid to form cocrystals and improve the solubility, dissolution, and bioavailability of poorly soluble telmisartan.

Gold nanoparticles and gold nanorods in the landscape of cancer therapy.

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line.

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, 13CNMR, and 1HNMR,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 µg/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Exploring the volatile metabolites of three Chorisia species: Comparative headspace GC-MS, multivariate chemometrics, chemotaxonomic significance, and anti-SARS-CoV-2 potential.

Chorisia (syn. Ceiba) species are important ornamental, economic, and medicinal plants that are endowed with a diversity of secondary metabolites; however, their volatile organic compounds (VOCs) have been scarcely studied. Therefore, this work explores and compares the headspace floral volatiles of three common Chorisia species, namely Chorisia chodatii Hassl., Chorisia speciosa A. St.-Hil, and Chorisia insignis H.B.K. for the first time. A total of 112 VOCs of varied biosynthetic origins were identified at different qualitative and quantitative ratios, encompassing isoprenoids, fatty acid derivatives, phenylpropanoids, and others. Flowers of the investigated species showed perceptibly differentiated volatile profiles, with those emitted by C. insignis being dominated by non-oxygenated compounds (56.69 %), whereas oxygenated derivatives prevailed among the volatiles of C. chodatii (66.04 %) and C. speciosa (71.53 %). The variable importance in the projection (VIP) in the partial least-squares-discriminant (PLS-DA) analysis described 25 key compounds among the studied species, of which linalool was verified as the most important aroma compound based on VIP values and significance analysis, and it could represent the most typical VOC among these Chorisia species. Furthermore, molecular docking and dynamics analyses of both the major and the key VOCs displayed their moderate to promising binding interactions with four main proteins of SARS-CoV-2, including Mpro, PLpro, RdRp, and spike S1 subunit RBD. The current results collectively cast new light on the chemical diversity of the VOCs of Chorisia plants as well as their chemotaxonomic and biological relevance.

New opportunities for RGD-engineered metal nanoparticles in cancer.

The advent of nanotechnology has opened new possibilities for bioimaging. Metal nanoparticles (such as gold, silver, iron, copper, etc.) hold tremendous potential and offer enormous opportunities for imaging and diagnostics due to their broad optical characteristics, ease of manufacturing technique, and simple surface modification. The arginine-glycine-aspartate (RGD) peptide is a three-amino acid sequence that seems to have a considerably greater ability to adhere to integrin adhesion molecules that exclusively express on tumour cells. RGD peptides act as the efficient tailoring ligand with a variety of benefits including non-toxicity, greater precision, rapid clearance, etc. This review focuses on the possibility of non-invasive cancer imaging using metal nanoparticles with RGD assistance.

An overview of topical lipid-based and polymer-based nanocarriers for treatment of psoriasis.

Psoriasis is a consistently recurring, inflammatory skin disease, affecting about 2-5 % of the world population. Different types of psoriasis can be observed such as guttate psoriasis, pustular psoriasis, psoriatic arthritis, scalp psoriasis, flexural psoriasis etc. Several therapeutic approaches are available for the treatment of psoriasis. However, none of them are entirely safe and effective to treat the disease without compromising patient compliance. The traditional treatment plan is associated with harmful side effects such asimmune system suppression and damage of essential organs at high doses, which poses a challenge to treat psoriasis. Novel drug delivery systems are being developed to replace traditional therapy in order to address these shortcomings. Currently, nanoformulations have gained widespread application for treatment of psoriasis. Researchers have developed different types of lipid-based nanoparticles like liposomes, niosomes, ethosomes, transethosomes, nanostructured lipid carriers and solid lipid nanoparticles. These innovative formulations provide advantages in terms of reduction in dose, dosing frequency, dose-dependency with enhanced efficacy, improved encapsulation efficiency, controlled release, increased surface area, high bioavailability and greater stratum corneum permeability. This review highlights detailed and comparative discussion of lipid-based and polymer-based nanoparticles for psoriasis along with the pathophysiology and other treatments of psoriasis.

Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19.

BACKGROUND: COVID-19 has been frequently demonstrated to be associated with anosmia. Calcium cations are a mainstay in the transmission of odor. One of their documented effects is feedback inhibition. Thus, it has been advocated that reducing the free intranasal calcium cations using topical chelators such as pentasodium diethylenetriamine pentaacetate (DTPA) could lead to restoration of the olfactory function in patients with post-COVID-19 anosmia. METHODOLOGY: This is a randomized controlled trial that investigated the effect of DTPA on post-COVID-19 anosmia. A total of 66 adult patients who had confirmed COVID-19 with associated anosmia that continued beyond three months of being negative for SARS-CoV-2 infection. The included patients were randomly allocated to the control group that received 0.9 % sodium chloride-containing nasal spray or the interventional group that received 2 % DTPA-containing nasal spray at a 1:1 ratio. Before treatment and 30 days post-treatment, the patients' olfactory function was evaluated using Sniffin' Sticks, and quantitative estimation of the calcium cations in the nasal mucus was done using a carbon paste ion-selective electrode test. RESULTS: Patients in the DTPA-treated group significantly improved compared to the control group in recovery from functional anosmia to hyposmia. Additionally, they showed a significant post-treatment reduction in the calcium concentration compared to the control group. CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.

Exploring Probenecid Derived 1,3,4-Oxadiazole-Phthalimide Hybrid as α-Amylase Inhibitor: Synthesis, Structural Investigation, and Molecular Modeling.

1,3,4-Oxadiazole moiety is a crucial pharmacophore in many biologically active compounds. In a typical synthesis, probenecid was subjected to a sequence of reactions to obtain a 1,3,4-oxadiazole-phthalimide hybrid (PESMP) in high yields. The NMR (1H and 13C) spectroscopic analysis initially confirmed the structure of PESMP. Further spectral aspects were validated based on a single-crystal XRD analysis. Experimental findings were confirmed afterwards by executing a Hirshfeld surface (HS) analysis and quantum mechanical computations. The HS analysis showed the role of the π⋯π stacking interactions in PESMP. PESMP was found to have a high stability and lower reactivity in terms of global reactivity parameters. α-Amylase inhibition studies revealed that the PESMP was a good inhibitor of α-amylase with an s value of 10.60 ± 0.16 µg/mL compared with that of standard acarbose (IC50 = 8.80 ± 0.21 µg/mL). Molecular docking was also utilized to reveal the binding pose and features of PESMP against the α-amylase enzyme. Via docking computations, the high potency of PESMP and acarbose towards the α-amylase enzyme was unveiled and confirmed by docking scores of -7.4 and -9.4 kcal/mol, respectively. These findings shine a new light on the potential of PESMP compounds as α-amylase inhibitors.

Nanocrystals as an emerging nanocarrier for the management of dermatological diseases.

Skin conditions are amongst the most prevalent health issues in the world and come with a heavy economic, social, and psychological burden. Incurable and chronic skin conditions like eczema, psoriasis, fungal infections are linked to major morbidity in the manner of physical pain and a reduction in quality life of patients. Several drugs have difficulties for penetrating the skin due to the barrier mechanism of the skin layers and the incompatible physicochemical characteristics of the drugs. This has led to the introduction of innovative drug delivery methods. Currently, formulations depend on nanocrystals have indeed been researched for topical administration of drugs and have resulted in enhanced skin penetration. This review focuses on skin penetration barriers, modern methods to enhance topical distribution, and the use of nanocrystals to overcome these barriers. By means of mechanisms such as adherence to skin, creation of diffusional corona, targeting of hair follicles, and the generation of a greater concentration gradient throughout the skin, nanocrystals could enhance transport across the skin. Scientists working on product formulations incorporating chemicals that are "challenging-to-deliver" topically may find the most current findings to be of relevance.

Ginger Extract-Loaded Transethosomes for Effective Transdermal Permeation and Anti-Inflammation in Rat Model.

Introduction: Ginger extract (GE) has sparked great interest due to its numerous biological benefits. However, it suffers from limited skin permeability, which challenges its transdermal application. The target of the current work was to develop transethosomes as a potential nanovehicle to achieve enhanced transdermal delivery of GE through the skin. Methods: GE-loaded transethosomes were prepared by cold injection using different edge activators. The fabricated nanovesicles were evaluated for particle size, ζ-potential, encapsulation efficiency, and in vitro drug release. The selected formulation was then laden into the hydrogel system and evaluated for ex vivo permeability and in vivo anti-inflammatory activity in a carrageenan-induced rat-paw edema model. Results: The selected formulation comprised of sodium deoxycholate exhibited particle size of 188.3±7.66 nm, ζ-potential of -38.6±0.08 mV, and encapsulation efficiency of 91.0%±0.24%. The developed transethosomal hydrogel containing hydroxypropyl methylcellulose was homogeneous, pseudoplastic, and demonstrated sustained drug release. Furthermore, it exhibited improved flux (12.61±0.45 µg.cm2/second), apparent skin permeability (2.43±0.008×10-6 cm/second), and skin deposition compared to free GE hydrogel. In vivo testing and histopathological examination revealed that the GE transethosomal hydrogel exhibited significant inhibition of edema swelling compared to free GE hydrogel and ketoprofen gel. The animals that were treated with ginger transethosome hydrogel showed a significant decrement in reactive oxygen species and prostaglandin E2 compared to untreated animals. Conclusion: Transethosomes might be a promising new vehicle for GE for effective skin permeation and anti-inflammation. To the best of our knowledge, this work is the first utilization of transethosomes laden into hydrogel as a novel transdermal delivery system of GE.

Promoter methylation might shift the balance of Galectin-3 & 12 expression in de novo adult acute myeloid leukemia patients.

Acute myeloid leukemia (AML) was reported as the most common type of leukemia among adults. Galectins constitute a family of galactose-binding proteins reported to play a critical role in many malignancies including AML. Galectin-3 and -12 are members of the mammalian galectin family. To understand the contribution of galectin-3 and -12 promoter methylation to their expression, we performed bisulfite methylation-specific (MSP)-PCR and bisulfite genomic sequencing (BGS) of primary leukemic cells in patients with de novo AML before receiving any therapy. Here, we show a significant loss of LGALS12 gene expression in association with promoter methylation. The lowest degree of expression was found in the methylated (M) group while the highest degree was in the unmethylated (U) group and the partially methylated (P) group expression lies in between. This was not the case with galectin-3 in our cohort unless the CpG sites analyzed were outside the frame of the studied fragment. We were also able to identify four CpG sites (CpG number 1, 5, 7& 8) in the promoter region of galectin-12; these sites must be unmethylated so that expression can be induced. As far as the authors know, these findings were not previously concluded in earlier studies.