Whiteness, redness, blueness and greenness profile assessment and design of experiments approach to microwave-aided sensitive and green spectrofluorophotometric determination of baclofen.

As a gamma amino butyric acid-ergic agonist, Baclofen is often prescribed to adults and children for the treatment of severe spasticity that originates in the brain or spinal cord. Even after reviewing the literature extensively, no one has documented a method for estimating baclofen using microwave-assisted stability-indicating spectrofluorimetric techniques, despite the abundance of options for baclofen stability, assay, and bioanalysis. Organic solvents, which are typically necessary for current procedures but may be costly and toxic, have a severe effect on aquatic life and the environment. Using green solvents and 4-chloro-7-nitrobezofuran as a fluorescent probe, this work conducted a stability-indicating spectrofluorimetric estimate of baclofen. Through the use of a design-of-experiments technique, a reliable microwave-aided spectrofluorimetric method was developed, with little solvent consumption and time for sample analysis. Prior to conducting response surface analysis and optimizing important variables and responses, a fractional factorial design was used to screen method variables and responses. A central composite design was then employed for these purposes. This flexible spectrofluorimetric technique was used to assess baclofen concentrations in forced degraded samples and marketed formulations. For baclofen determination, the suggested spectrofluorimetric approach was found to be green, quick, easy to use, economical, and user-friendly.

Lipid-based nanoparticles: innovations in ocular drug delivery.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

A novel mucoadhesive paliperidone-nanoemulsion developed using the ultrasonication method in the treatment of schizophrenia.

Aim: To develop paliperidone mucoadhesive-nanoemulsion (PLP-NE) to enhance brain bioavailability. To evaluate comparative effects of PLP-NE and CS-PLP-NE in the treatment of schizophrenia, followed by a toxicity study of opt-NE. Material and methods: Oil: oleic acid, surfactant: Tween-80, and co-surfactant: Labrasol were chosen based on the solubility and maximum nanoemulsion area. The ultrasonication technique was applied with the aqueous micro titration method for the development of PLP-NE. The optimization of the method for the excellent PLP-NE was performed using a central composite design based on a five-factor and four-level. Oil (% v/v), S mix (v/v%), ultrasonication intensity in percentage, ultrasonication time in minutes, and temperature (°C) were optimized and used to the independent variables. Results: The parameters i.e., oil (5%), S mix (10%), ultrasonication time (5.0 min), ultrasonication intensity (25%), and temperature (38 °C) were optimized and used as independent and dependent variables for the development of novel PLP-NE. Based on experimental data, the dependent variables, i.e., globule size (53.90 ± 4.01 nm), % transmittance (92.56% ± 1.06%), PDI (0.218 ± 0.007), and zeta potential (-11.60 ± 0.031 mV), were determined. The smooth near about spherical shaped of PLP-NE globules with, refractive index i.e., 1.62 ± 0.021, viscosity: 39 ± 6 cp with the pH: 7.40 ± 0.089, and content of drug (97.98 ± 0.39%) for optimized-PLP-NE. The optimized PLP-NE with oleic acid, Tween-80, and Labrasol was used to improve brain bioavailability with good permeation via the intranasal route. CS-PLP-NE yielded good mucoadhesive property results compared to paliperidone-nanoemulsion, and PLP-S containing a 0.751 minutes retention time with their deuterated-IS (0.806 min) and m/z of 427.2/207.2 with IS (m/z: 431.2/211.2) for PLP and PLP-IS. A calibration curve was plotted with a linear range of 1-2000 ng mL-1 with inter- and intraday accuracy (97.03-99.31%) and precision (1.69-50.05%). The results of AUC(0-24) and C max for PLP were found to be highly significant (p < 0.001) as an improvement of brain bioavailability in rats via intranasal delivery of CS-PLP-NE. Furthermore, the locomotion test, social interaction, and forced swimming test (forced swimming, climbing, and immobility) of a mucoadhesive CS-PLP-NE (intranasally) provided highly significant results with the improvement of behavioral analysis when compared to the PLP-NE and PLP-S studies. Conclusion: CS-PLP-NE (i.n.) showed highly significant results, i.e., p < 0.001 for the improvement of bioavailability of the brain in the treatment of schizophrenia. Optimized-mucoadhesive-CS-based-PLP-NE is safe and shows no toxicity.

Targeting protein receptors and enzymes for precision management of urolithiasis: A comprehensive review.

Urolithiasis, characterized by the formation of solid crystalline structures within the urinary tract, presents a significant global health burden with high recurrence rates and limited treatment efficacy. Recent research has identified various protein receptors and enzymes implicated in the pathogenesis of urolithiasis, offering potential targets for therapeutic intervention. Protein receptors such as the calcium-sensing receptor and vasopressin V2 receptor play crucial roles in regulating urinary calcium excretion and water reabsorption, respectively, influencing stone formation. Additionally, modulation of receptors like the angiotensin II receptor and aldosterone receptor can impact renal function and electrolyte balance, contributing to stone prevention. Furthermore, enzymes such as urease inhibitors and xanthine oxidase inhibitors offer targeted approaches to prevent the formation of specific stone types. This review discusses the potential of targeting these receptors and enzymes for the treatment of urolithiasis, exploring associated drugs and their mechanisms of action. Despite promising avenues for personalized and precision medicine approaches, challenges such as the need for robust clinical evidence and ensuring cost-effectiveness must be addressed for the translation of these interventions into clinical practice. By overcoming these challenges, receptor-targeted therapies and enzyme inhibitors hold promise for revolutionizing the management of urolithiasis and reducing its global burden.

In-vivo pharmacokinetic study of ibrutinib-loaded nanostructured lipid carriers in rat plasma by sensitive spectrofluorimetric method using harmonized approach of quality by design and white analytical chemistry.

Ibrutinib, an antineoplastic agent tackling chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia, falls under the category of BCS class II drugs, characterized by a puzzling combination of low solubility and high permeability. Its oral bioavailability remains a perplexing challenge, merely reaching 2.9 % due to formidable first-pass metabolism hurdles. In a bid to surmount this obstacle, researchers embarked on a journey to develop ibrutinib-loaded NLCs (Nanostructured Lipid Carriers) using a methodology steeped in complexity: a Design of Experiments (DoE)-based hot melted ultrasonication approach. Despite a plethora of methods for analyzing ibrutinib in various matrices, the absence of a spectrofluorimetric method for assessing it in rat plasma added to the enigma. Thus emerged a spectrofluorimetric method, embodying principles of white analytical chemistry and analytical quality by design, employing a Placket-Burman design for initial method exploration and a central composite design for subsequent refinement. This method underwent rigorous validation in accordance with ICH guidelines, paving the way for its application in scrutinizing the in-vivo pharmacokinetics of ibrutinib-loaded NLCs, juxtaposed against commercially available formulations. Surprisingly, the optimized NLCs exhibited a striking 1.82-fold boost in oral bioavailability, shedding light on their potential efficacy. The environmental impact of this method was scrutinized using analytical greenness tools, affirming its eco-friendly attributes. In essence, the culmination of these efforts has not only propelled advancements in drug bioavailability but also heralded the dawn of a streamlined and environmentally conscious analytical paradigm.

Integrated approach of white analytical chemistry and design of experiments to microwave-assisted sensitive and eco-friendly spectrofluorimetric estimation of mirabegron using 4-chloro-7-nitrobezofuran as biosensing fluorescent probe.

The USFDA recently approved mirabegron, a novel once-daily ß-3 adrenoceptor agonist for oral administration, as a transformative treatment for overactive bladder. Despite the existence of numerous analytical methods for the assay and bioanalysis of mirabegron, it's perplexing that none have explored the domain of microwave-assisted sensitive spectrofluorimetric method for mirabegron estimation, even after extensive literature review. Adding to the enigma is the insistence of current analytical methods on using expensive and harmful organic solvents, posing a threat to marine life and the broader environment. Recently, the white analytical chemistry approach has been introduced to develop analytical methods that are cost-effective, environmentally friendly, and user-friendly. Consequently, a white analytical chemistry-based, sensitive, and eco-friendly spectrofluorimetric estimation of mirabegron has been initiated, using 4-Chloro-7-nitrobenzofurazan as a fluorescent biosensing probe. The development of this robust method involved a series of experiments designed to minimize solvent and time wastage. Through a combination of fractional factorial and Box-Behnken designs, researchers identified the critical variables and optimized the method to perfection. This method was validated according to the stringent ICH Q2 (R2) and USFDA guidelines, ensuring its reliability and accuracy. Once approved, this sensitive spectrofluorimetric method was tested, accurately estimating mirabegron levels in commercial formulations and rat plasma samples. To further enrich the study, a comprehensive evaluation of existing analytical methods was conducted alongside the proposed spectrofluorimetric method, using advanced tools like the AGREE calculator, GAPI software, and RGB model to assess their eco-friendliness and effectiveness in mirabegron estimation.

Significance of Triazole in Medicinal Chemistry: Advancement in Drug Design, Reward and Biological Activity.

One of the triazole tautomers, 1,2,4-triazole derivatives, has a wide range of biological activities that suggest its potential therapeutic utility in medicinal chemistry. These actions include anti-inflammatory, anti-cancer, anti-bacterial, anti-tuberculosis, and anti-diabetic effects. Using computational simulations and models, we investigate the structure-activity relationships of 1,2,4-triazoles, showing how various modifications to the triazole core yield a variety of clinical therapeutic benefits. The review highlights the anti-inflammatory effect of 1,2,4-triazoles in relation to their ability to disrupt significant inflammatory mediators and pathways. We present in-silico data that illuminate the triazoles' capacity to inhibit cell division, encourage apoptosis, and stop metastasis in a range of cancer models. This review looks at the bactericidal and bacteriostatic properties of 1,2,4-triazole derivatives, with a focus on their potential efficacy against multi-drug resistant bacterial infections and their usage in tuberculosis therapy. In order to better understand these substances' potential anti-diabetic benefits, this review also looks at how they affect glucose metabolism regulation and insulin responsiveness. Coordinated efforts are required to translate the efficacy of 1,2,4-triazole compounds in preclinical models into practical therapeutic benefits. Based on the information provided, it can be concluded that 1,2,4-triazole derivatives are a promising class of diverse therapeutic agents with potential utility in a range of disorders. Their development and improvement might herald a new era of medical care that will be immensely advantageous to both patients and the medical community as a whole. This comprehensive research, which is further reinforced by in-silico investigations, highlights the great medicinal potential of 1,2,4-triazoles. Additionally, this study encourages more research into these substances and their enhancement for use in pharmaceutical development.

Synthesis, molecular docking, and in vivo antidiabetic evaluation of new benzylidene-2,4-thiazolidinediones as partial PPAR-γ agonists.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) partial agonists or antagonists, also termed as selective PPAR-γ modulators, are more beneficial than full agonists because they can avoid the adverse effects associated with PPAR-γ full agonists, such as weight gain and congestive heart disorders, while retaining the antidiabetic efficiency. In this study, we designed and synthesized new benzylidene-thiazolidine-2,4-diones while keeping the acidic thiazolidinedione (TZD) ring at the center, which is in contrast with the typical pharmacophore of PPAR-γ agonists. Five compounds (5a-e) were designed and synthesized in moderate to good yields and were characterized using spectral techniques. The in vivo antidiabetic efficacy of the synthesized compounds was assessed on streptozotocin-induced diabetic mice using standard protocols, and their effect on weight gain was also studied. Molecular docking and molecular dynamics (MD) simulation studies were performed to investigate the binding interactions of the title compounds with the PPAR-γ receptor and to establish their binding mechanism. Antidiabetic activity results revealed that compounds 5d and 5e possess promising antidiabetic activity comparable with the standard drug rosiglitazone. No compound showed considerable effect on the body weight of animals after 21 days of administration, and the findings showed statistical difference (p < 0.05 to p < 0.0001) among the diabetic control and standard drug rosiglitazone groups. In molecular docking study, compounds 5c and 5d exhibited higher binding energies (- 10.1 and - 10.0 kcal/mol, respectively) than the native ligand, non-thiazolidinedione PPAR-γ partial agonist (nTZDpa) (- 9.8 kcal/mol). MD simulation further authenticated the stability of compound 5c-PPAR-γ complex over the 150 ns duration. The RMSD, RMSF, rGyr, SASA, and binding interactions of compound 5c-PPAR-γ complex were comparable to those of native ligand nTZDpa-PPAR-γ complex, suggesting that the title compounds have the potential to be developed as partial PPAR-γ agonists.

An intact amber-free HIV-1 system for in-virus protein bioorthogonal click labeling that delineates envelope conformational dynamics.

The HIV-1 envelope (Env) glycoprotein is conformationally dynamic and mediates membrane fusion required for cell entry. Single-molecule fluorescence resonance energy transfer (smFRET) of Env using peptide tags has provided mechanistic insights into the dynamics of Env conformations. Nevertheless, using peptide tags risks potential effects on structural integrity. Here, we aim to establish minimally invasive smFRET systems of Env on the virus by combining genetic code expansion and bioorthogonal click chemistry. Amber stop-codon suppression allows site-specifically incorporating noncanonical/unnatural amino acids (ncAAs) at introduced amber sites into proteins. However, ncAA incorporation into Env (or other HIV-1 proteins) in the virus context has been challenging due to low copies of Env on virions and incomplete amber suppression in mammalian cells. Here, we developed an intact amber-free virus system that overcomes impediments from preexisting ambers in HIV-1. Using this system, we successfully incorporated dual ncAAs at amber-introduced sites into Env on intact virions. Dual-ncAA incorporated Env retained similar neutralization sensitivities to neutralizing antibodies as wildtype. smFRET of click-labeled Env on intact amber-free virions recapitulated conformational profiles of Env. The amber-free HIV-1 infectious system also permits in-virus protein bioorthogonal labeling, compatible with various advanced microscopic studies of virus entry, trafficking, and egress in living cells. Amber-free HIV-1 infectious systems actualized minimal invasive Env tagging for smFRET, versatile for in-virus bioorthogonal click labeling in advanced microscopic studies of virus-host interactions.

Synthesis, in-Silico studies and biological evaluation of pyrimidine based thiazolidinedione derivatives as potential anti-diabetic agent.

Despite the advancements in the management of Diabetes mellitus, the design and synthesis of drug molecule which ameliorates the hyperglycemia and associated secondary complications in diabetic patients, still remains a challenge. Herein, we report the synthesis, characterization and anti-diabetic evaluation of pyrimidine-thiazolidinedione derivatives. The synthesized compounds were characterized by 1H NMR, 13C NMR, FTIR and Mass Spectroscopic analytical techniques. The in-silico ADME studies depicted that the compounds were within the permissible limits of the Lipinski's rule of five. The compounds 6e and 6m showing the best results in OGTT were evaluated for in-vivo anti-diabetic evaluation in STZ induced diabetic rats. Administration of 6e and 6m for four weeks decreased the blood glucose levels significantly. Compound 6e (4.5 mg/kg p.o.) was the most potent compound of the series. It reduced the level of blood glucose to 145.2 ± 1.35 compared to the standard Pioglitazone (150.2 ± 1.06). Moreover, the 6e and 6m treated group did not show increase in bodyweight. The biochemical estimations showed that the levels of ALT, ASP, ALP, urea, creatinine, blood urea nitrogen, total protein and LDH restored to normal in 6e and 6m treated groups as compared to STZ control group. The histopathological studies supported the results obtained in biochemical estimations. Both the compounds did not show any toxicity. Moreover, the histopathological studies of pancreas, liver, heart and kidney revealed that the structural integrity of these tissues restored to almost normal in 6e and 6m treated groups as compared to STZ control group. Based upon these findings it can be concluded that the pyrimidine-based thiazolidinedione derivatives represent novel anti-diabetic agents with least side effects.

The Structural, Biological, and In-Silico Profiling of Novel Capryloyl Tetra-Glucoside and Aliphatic Ester Constituents from the Abutilon indicum Offers New Perspectives on the Treatment of Pain and Inflammation.

Abutilon indicum L. (Malvaceae), more often referred to as Peeli booti, Kanghi, and Kakhi, is a perennial shrub found in many countries of Asia. Traditionally, this plant is used as a diuretic to treat inflammation, discomfort, urethral infections, and gout. Inflammation and pain are key topics of interest for researchers throughout the globe, since they are linked to almost every illness that could affect humans or animals. The present study was conducted to isolate the phytoconstituents from the methanolic extract of Abutilon indicum collected from the Bihar state Koshi river belt in India, and to evaluate the isolated phytoconstituents' ability to reduce nociception and inflammation. Furthermore, molecular docking was performed to investigate the molecular interaction profile, with possible therapeutic targets for anti-inflammatory medicines. A. indicum methanolic extract yielded two novel phytocompounds identified as 5'-hydroxyhexyl n-hexadecanoate (AB-01) and n-octanoyl-ß-D-glucopyranosyl-(2'-1'')-ß-D-glucopyranosyl-(2''-1''')-ß-D-glucopyranosyl-(2'''-1'''')-ß-D-glucopyranoside (AB-05), together with three previously recognized phytocompounds such as ester glucoside. All isolated molecules were tested for the efficacy of analgesic and anti-inflammatory characteristics at doses of 5 and 10 mg/kg body weight. The isolated compound's molecular interaction profile with anti-inflammatory drug targets cyclooxygenase-2 and tumor necrosis factor-alpha possessed high potential energy in molecular docking. These findings may aid in developing anti-inflammatory and analgesic drugs from A. indicum.

Synthesis, biological evaluation and docking studies of methylene bearing cyanopyrimidine derivatives possessing a hydrazone moiety as potent Lysine specific demethylase-1 (LSD1) inhibitors: A promising anticancer agents.

A series of novel cyanopyrimidine-hydrazone hybrids were synthesized and characterized with various spectroscopic techniques. The synthesized compounds were tested at NCI, USA, on a 60-cell line panel and most of the compounds showed remarkable cytotoxic activity against different cancer cell lines. Compound 5a was found to be the most potent compound of the series and it was further selected for five dose assays wherein it exhibited GI50 value of 0.414 µM and 0.417 µM against HOP-62 and OVCAR-4 cell lines respectively. The in-silico mechanistic studies indicated that these compounds are acting through inhibition of lysine specific demethylase 1 (LSD1) as evident from in to vitro LSD1 inhibition activity of compounds. Among various synthesized derivatives, compound 5a was found to have IC50-value of 0.956 µM. In addition, absorption, distribution, metabolism, excretion and toxicity profile (ADMET) was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes which revealed that synthesized compounds showed acceptable metabolic stability in human liver microsomes with minimal inhibition of cytochrome P450s (CYPs). The results indicated that compound 5a could be a promising lead compound for further development as a therapeutic agent for anticancer activity.

Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents.

BACKGROUND: The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic. METHODS: The main protease (Mpro) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation. RESULTS: Out of 1397 potential drugs, 157 showed considerable affinity toward Mpro. After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies -10.629 to -11.776kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (-73.800kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against Mpro. All aminoglycosides were bound to the substrate-binding site of Mpro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of Mpro. MD simulations of the Amikacin-Mpro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions. CONCLUSION: Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent.

Emerging advances in cationic liposomal cancer nanovaccines: opportunities and challenges.

Advancements in the field of cancer therapeutics have witnessed a recent surge in the use of liposomes. The physicochemical characteristics of the liposomes and their components, including the lipid phase transition temperature, vesicular size and size distribution, surface properties, and route of administration, play a significant role in the modulation of the immune response as an adjuvant and for loaded antigen (Ag). Cationic liposomes, concerning their potential ability to amplify the immunogenicity of the loaded Ag/adjuvant, have received enormous interest as a promising vaccine delivery platform for cancer immunotherapy. In the present review, the physicochemical considerations for the development of Ag/adjuvant-loaded liposomes and the cationic liposomes' effectiveness for promoting cancer immunotherapy have been summarized.

QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation.

Azacitidine (AZA), an inhibitor of DNA methyltransferase, is a commonly recognized drug used in clinical treatment for myelodysplastic syndrome and breast cancer. Due to higher aqueous solubility and negative log P of AZA causes poor cancer cell permeation and controlled release. The objective of the present study was to formulate and optimize AZA-loaded liposome (AZA-LIPO) for breast cancer chemotherapy by using Box Behnken design (BBD) and in vitro evaluation using MCF-7 cells. AZA-LIPO were prepared using a thin film hydration technique and characterization study was performed by using FTIR and DSC. The prepared formulations were optimized using BBD and the optimized formulation was further subjected for particle size, surface charges, polydispersity index (PDI), drug loading, entrapment efficiency, TEM, XRD, in-vitro drug release and hemolytic toxicity. The mean particle size of optimized AZA-LIPO was 127 nm. Entrapment efficiency and drug loading of AZA-LIPO was found to be 85.2% ± 0.5 and 6.82 ± 1.6%, respectively. Further, in vitro drug release study showed preliminary burst release in 2 h followed by a sustained release for 36 h in phosphate buffer at different pH (4.0, 5.5, and 7.4) as compared to free drug. Drug release was found to be pH dependent, as the pH was increased, the drug release rate was found to be low. Time-dependent cell viability assay exhibited significant higher cell viability and higher internalization than free AZA in MCF-7 cells. AZA-LIPO were more effective than the free AZA in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. The result showed that the formulated biocompatible AZA-LIPO nano-formulations may be used as an efficient anti-cancer drug delivery system for the treatment of breast cancer after establishing preclinical and clinical studies.

Solvent extraction, spectral analysis and antibacterial activity of the bioactive crystals of Sargassum aquifolium (Turner) C.Agardh from Red Sea.

The purpose of this study was to investigate the chemical composition and anti-bacterial properties of the bioactive principles of Sargassum aquifolium (Turner) C.Agardh, a brown seaweed in Red sea of Jazan province, Kingdom of Saudi Arabia. Crystals were obtained from the petroleum ether extract of Sargassum aquifolium and subjected to chemical tests, FTIR spectroscopic analysis and NMR analysis to identify their chemical composition, and to study their antibacterial properties against selected human pathogenic bacteria. In addition, GC-MS analysis was performed to identify the bioactive compounds in the crude petroleum ether extract. Results of the antibacterial effect of the crystal analyte showed a wide spectrum of activity against the screened human pathogenic bacteria.

Emerging advances in synthetic cancer nano-vaccines: opportunities and challenges.

Introduction: Cancer immunotherapy is a fast-growing field that has achieved tremendous progress in recent years. It is one of the most potent tools that can activate the immune system against cancer. Nevertheless, the development of safe and effective vaccines to overcome emerging new disease remains challenging since several emerging antigens are poorly immunogenic. Nanotechnology has provided a realistic resolution for the drawback of traditional cancer immunotherapy. Area covered: This review discusses different cancer immunotherapy approaches focusing on recent advancements in nanomedicine-based cancer immunotherapy. The literature review method includes inclusion and exclusion criteria to categorize important articles. The literature survey was carried out using PubMed, Google Scholar, Scopus, and the Saudi digital library. Expert opinion: In the last two decades, the development and application of nanoparticles incorporating antigen/adjuvant in cancer immunotherapy have experienced rapid growth. Soon, progressively multifaceted nanovaccines presenting different antigens and co-delivered with antigens will be clinically translated. Better understanding and improved knowledge of nanomedicines-based delivery approaches and immunostimulatory action, and in-vivo biodistribution would inevitably facilitate the altruistic design of cancer nanovaccine for humankind.

Development and characterization of Brigatinib loaded solid lipid nanoparticles: In-vitro cytotoxicity against human carcinoma A549 lung cell lines.

Brigatinib (BG) is a tyrosine kinase receptor inhibitor act as an antineoplastic agent by blocking the action of an abnormal protein that causes cancer cells to multiply. In the current study, nine formulae of BG loaded solid lipid nanoparticles (SLNs) were developed using 32 factorial design. SLNs were prepared by the solvent emulsification technique using stearic acid as lipid and soya- lecithin as a surfactant, both of these act as independent variables, whereas Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and drug loading (DL) were selected as responses. The particle size was found to be in the nano range (176-787 nm), fairly monodisperse (PDI indices 0.19-0.5), interparticle electrical stability was supported by zeta-potential (+1.78 mV to -15.4 mV), whereas EE and DL were in the range of (61.31-87.87 %) (3.35-31.01 %), respectively. Differential scanning calorimetry (DSC) thermograms indicated the amorphous state of BG in the SLN. Fourier transform infrared spectroscopy (FTIR) spectrums confirm non-interaction between drug and polymer while nuclear magnetic resonance (NMR) spectroscopy study revealed BG incorporation in the SLN. A scanning electron microscope (SEM) image exhibit a spherical shape of SLN. The in-vitro release profile demonstrates a sustained release pattern for the selected BS5 SLNs. MTT assay was performed on the optimized SLNs (BS5) and the results are indicative that BG loaded SLN (BS5) showed better cytotoxicity against A349 lung cell lines while compared to BG suspension and blank SLN. Thus, BG loaded SLNs can find Its better place in the non-small cell lung cancer treatment.

The Spectrum of Thiazolidinediones against Respiratory Tract Pathogenic Bacteria: An In Vitro and In Silico Approach.

BACKGROUND AND OBJECTIVES: Drug design strategies to develop novel broad-spectrum antibacterial agents for the treatment of respiratory tract infections that can combat bacterial resistance are currently gaining momentum. 2,4-thiazolidinedione is a structural scaffold that contains pharmacophores similar to ß-lactam and non- ß-lactam antibiotics. The objective of the study was to synthesize newer 3,5-Disubstituted-2,4-Thiazolidinediones (DTZDs) and subject them to in vitro antibacterial screening against bacterial pathogens. Also, we performed in silico docking of selected compounds to penicillin-binding proteins and beta-lactamases. METHODS: Intermediate Schiff bases were prepared by the reaction between 2,4-thiazolidinedione and an appropriate aldehyde followed by acylation of the ring nitrogen with 3-brompropanoyl chloride resulting in DTZDs. Minimum inhibitory concentrations were determined against few bacteria infecting the respiratory tract by the broth tube dilution method. Zones of inhibitions against the bacteria were also determined using agar well diffusion technique. Molecular docking of the compounds to all types of Penicillin-Binding Proteins (PBPs) and ß-lactamases was also carried out. RESULTS: Compounds DTZD12 and DTZD16 exhibited broad-spectrum antibacterial activity. The minimum inhibitory concentrations of the compounds were 175µg/100µL. Measurements of the zones of inhibitions indicated that compound DTZD12 was more active than DZTD16. E. coli was the most susceptible organism. Docking results established that both the compounds were able to interact with PBPs and ß-lactamases through strong hydrogen bonds, especially the unique interaction with active serine residue of the PBP for inhibition of cell wall synthesis. CONCLUSION: DTZD12 and DTZD16 can be developed into antibacterial drugs for respiratory tract infections to oppose bacterial resistance, or can also be used as leads for repurposing the existing 2,4- thiazolidinediones.

Response surface methodology-based optimization of ultrasound-assisted extraction of β-sitosterol and lupeol from Astragalus atropilosus (roots) and validation by HPTLC method

Objective: To optimize the ultrasonication method for efficient extraction of β-sitosterol and lupeol from the roots of Astragalus atropilosus using Box-Behnken design of response surface methodology (RSM), and its validation by high performance thin layer chromatography (HPTLC) method.Methods: Ultrasonication method was used to extract β-sitosterol and lupeol from Astragalus atropilosus (roots). RSM was used to optimize the different extraction parameters viz. liquid to solid ratio (10–14 mL/g), temperature (60-80 ℃) and time (40–60 min) to maximize the yield of β-sitosterol and lupeol. The quantitative estimation of β-sitosterol and lupeol was done in chloroform extract of Astragalus atropilosus by validated HPTLC method on 10 cm × 20 cm glass-backed silica gel 60F254 plate using hexane and ethyl acetate (8:2, v/v) as mobile phase. Results: A quadratic polynomial model was found to be most appropriate with regard to R1 (yield of total extraction; R2/％ CV = 0.9948/0.28), R2 (β-sitosterol yield; R2/％ CV = 0.9923/0.39) and R3 (lupeol yield; R2/％ CV = 0.9942/0.97). The values of adjusted R2/predicted R2/signal to noise ratio for R1, R2, and R3 were 0.9782/0.9551/48.77, 0.9904/0.9110/31.33, and 0.9927/0.9401/36.08, respectively, indicating a high degree of correlation and adequate signal. The linear correlation plot between the predicted and experimental values for R1, R2, and R3 showed high values of R2 ranging from 0.9905-0.9973. β-sitosterol and lupeol in chloroform extract of Astragalus atropilosus were detected at Rf values of 0.22 and 0.34, respectively, at λ max = 518 nm. The optimized ultrasonic extraction produced 8.462％ w/w of R1, 0.451％ w/w of R2 and 0.172％ w/w of R3 at 13.5 mL/g liquid to solid ratio,78 ℃ of temperature and 60 min of time.Conclusions: The experimental findings of RSM optimized extraction and HPTLC analysis can be further applied for the efficient extraction of β-sitosterol and lupeol in other species of Astragalus.