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Abstract The production of fine particles by green technology like supercritical carbon dioxide requires the assessment of substantial solubility data at high pressures. This study represents the first determination of the solubility of methyldopa in carbon dioxide at pressures and temperatures ranging from 12 to 30 MPa and from 313.2 to 343.2 K, respectively. The mole fractions were obtained under the aforementioned conditions and ranged from 0.805 × 10⁻5 to 11.345 × 10⁻5. Four empirical models (Chrastil, Bartle et al., Mendez-Santiago, & Teja, and Kumar-Johnston) and two equations of state (Peng-Robinson and Soave-Redlich-Kwong) were used to correlate drug solubility. The K-J model demonstrated the highest accuracy, with an AARD of 8.38% and a R2 value of 0.988. Furthermore, the enthalpy values for the drug in SC-CO₂ were estimated using the Chrastil and Bartle models, resulting in values of 34.35 and 56.87 kJ·mol⁻¹, respectively. The results demonstrate that the SRK more pronounced results than the PR model, with an AARD% of 23.03 and a R2 value of 0.903 compared to 26.42 and 0.837. The article’s conclusions provide a valuable reference for the application of green method in the production of fine particles of methyldopa.

Abstract In the present study, the solubility of sulfasalazine in carbon dioxide was investigated at temperatures ranging from 313 K to 343 K and pressures ranging from 12 to 30 MPa. The experimentally determined molar solubilities of sulfasalazine in ScCO2 were found to be in the range of 4.08 × 10− 5 to 8.61 × 10− 5 at 313 K, 3.54 × 10− 5 to 11.41 × 10− 5 at 323 K, 3.04 × 10− 5 to 13.64 × 10− 5 at 333 K, and 2.66 × 10− 5 to 16.35 × 10− 5 at 343 K. The solubility values were correlated via a number of different types of equations, such as semi-empirical correlations, the Peng-Robinson, the PC-SAFT equation, and the regular solution. Furthermore, the findings demonstrate that semi-empirical, equation of state models, and the regular solution model possess the capability of precisely determining the solubility. Moreover, the solubility magnitude suggests that the gas anti-solvent method may be a viable approach for nanoparticle production.

Abstract: Background The human erect posture has been linked to the iliotibial band, also known as Maissiat’s band. The ITB is a fibrous and tough fascial tissue that extends from the iliac crest to the lateral proximal tibia. Increased tension or stiffness in the iliotibial band is referred to as ITB tightness. Flexibility is a critical element needed for optimal musculoskeletal function and enhancing physical activity performance. People deal with the ubiquitous issue of flexibility dysfunction. In addition to being a contributing factor to a reduced range of motion, muscle tightness it can also signal other orthopedic issues. Objective: To investigate the association between prolonged cross-legged sitting with IT band tightness among university students. Methodology: In this study prolonged cross-legged sitting duration was set for about 1 hr. - 5 hrs. in a day. 266 university students aged 20-27, who regularly cross-legged were included. Data was collected using a self-made questionnaire. Results: The results revealed that out of all participants, 16.9 % spend 1-2, 26.7% spend 2-3 hours, 27.1 % spend 3-4 hours, while 29.3% spend 4-5 hours seated cross-legged in a day. The Chi-square p-value of 0.077 indicates that there is no statistically significant association between the number of hours spent sitting cross-legged in university and the results of Ober’s test. Conclusion: In conclusion, the study shows that increasing iliotibial band tightness is not caused by prolonged periods of cross-legged sitting in university students. Keywords: Cross-legged sitting, ITB, long sitting hours, university students, tightness

Nitrosamine impurities identified in several pharmaceuticals during recent times has raised concerns leading to product recalls worldwide and necessitating sensitive liquid and gas chromatographic methods for trace level detection of nitrosamine impurities. This study developed and validated a ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the quantification of NDMA in Levosulpuride drug substance and tablet formulation. Current method utilizes a triple quadrupole analyzer, atmospheric pressure chemical ionization (APCI) ionization source and multiple reaction monitoring (MRM) scan mode for the analysis. Chromatographic separation was achieved on a Gemini NX-C18 column (150 × 4.6 mm, 3 µm) maintained at 40 °C. The mobile phase consisted of a binary gradient of solvent A (0.1 % formic acid in water) and solvent B (methanol), with a total run time of 18 minutes. Current method achieved excellent linearity, recovery, precision, and sensitivity. Greenness of the developed method was evaluated using the GAPI, AGREE, and AES metrics. Current method is sensitive and selective for NDMA in levosulpuride drug substance and tablet formulations and can be employed for routine quality control analysis in pharmaceutical industry.

Abstract Colorectal cancer, the third most prevalent cancer globally, contributes significantly to mortality rates, with over 1.9 million reported cases and nearly 935,000 fatalities annually. Surgical resection is a primary approach for localized colorectal tumors, with adjunct therapies like chemotherapy, radiotherapy, and targeted/immunotherapy considered depending on the tumor stage. However, despite preferences for targeted and immunotherapy post-surgery, chemotherapy remains commonly chosen due to its lower cost and high cancer-killing efficiency. Yet, chemotherapy faces issues such as tumor resistance and severe side effects. Nanotechnology has emerged in cancer therapy by alleviating the drawbacks of current treatment approaches. In the past few decades, inorganic nanoparticles have shown promise in combating colorectal cancer, offering advantages over conventional chemotherapy. Compared to organic nanoparticles, inorganic nanoparticles exhibit properties like photosensitivity, conductivity, magnetic allure, and thermal proficiency, allowing them to function as both drug carriers and therapeutic agents. Derived primarily from carbon, silica, metals, and metal oxides, they offer superior drug-loading capacity, heightened quantum yield, and participation in advanced photothermal and photodynamic therapies. This review provides a brief overview of the pathophysiology of colorectal cancer and the pivotal role of inorganic nanoparticles in photothermal therapy photodynamic therapy, and drug delivery. Additionally, it discusses numerous inorganic nanoparticles in colorectal cancer therapy based on recent literature. Graphical abstract

The solubility of ivermectin in high pressure carbon dioxide (CO2) at 338, 328, 318, and 308 K temperatures was investigated with and without an ethanol. Several methods were employed to model the data obtained from the experiments. ivermectin exhibited solubility values ranging from 0.130 × 10−5 to 1.760 × 10−4 in the binary system and 1.880 × 10−5 to 1.237 × 10−4 in the ternary system. The outcome indicated that the addition of ethanol significantly increased the mole fraction of ivermectin in CO2. The highest impact of ivermectin solubility was found in the ivermectin -Ethanol- CO2 system at 338 K and 12 MPa, which was about 14.35 times greater than binary system under the same conditions. The models proposed by Jouyban et al. and Sodeifian-Sajadian models showed the best correlation with average absolute relative deviation (AARD%) and Akaike information criterion (AICc) for binary and ternary approaches, respectively. The results confirmed that rapid expansion supercritical solution (RESS) and gas antisolvent (GAS) method can be apply for producing nanoparticles at the suitable ranges of the drug solubility.

Background: Psoriatic arthritis (PsA), a chronic inflammatory disease, mainly affects the joints, with approximately 30% of psoriasis patients eventually developing PsA. Characterized by both innate and adaptive immune responses, PsA poses significant challenges for effective treatment. Recent advances in drug delivery systems have sparked interest in developing novel formulations to improve therapeutic outcomes. The current research focuses on the development and evaluation of a nanosponge-loaded, cyclo-oxygenase-2 (COX-2) inhibitor-based topical gel for the treatment of PsA. Methods: Nanosponges (NSs) were prepared by using beta-cyclodextrin as a polymer and dimethyl carbonate (DMC) as a crosslinker by melting, and gels were prepared by employing carbopol and badam gum as polymers. Results: Solubility studies confirmed that the prepared nanosponges were highly soluble. FT-IR studies confirmed the formation of hydrogen bonds between lumiracoxib and beta-cyclodextrin. SEM confirmed that the prepared formulations were roughly spherical and porous in nature. The average particle size was 190.5 ± 0.02 nm, with a zeta potential of −18.9 mv. XRD studies showed that the crystallinity of lumiracoxib decreased after encapsulation, which helped to increase its solubility. The optimized nanosponges (NS2) were incorporated in an optimized gel (FG10) to formulate a nanosponge-loaded topical gel. The optimized gel formulation exhibited a homogeneous consistency, with a pH of 6.8 and a viscosity of 1.15 PaS, indicating its suitability for topical application and stability. The in vitro diffusion studies for the topical gel showed drug release of 82.32% in 24 h. The optimized formulation demonstrated significant antipsoriatic activity, as confirmed through cytotoxicity studies conducted on HaCaT cells. Conclusions: On the basis of the findings, it can be concluded that the prepared nanosponge-loaded topical gel formulation presents a promising solution for the effective management of PsA, offering enhanced drug solubility, sustained release, and improved therapeutic potential.

Cancer, the most common condition worldwide, ranks second in terms of the number of human deaths, surpassing cardiovascular diseases. Uncontrolled cell multiplication and resistance to cell death are the traditional features of cancer. The myriad of treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy to treat this disease. Conventional chemotherapy drug delivery suffers from issues such as the risk of damage to benign cells, which can cause toxicity, and a few tumor cells withstand apoptosis, thereby increasing the likelihood of developing tolerance. The side effects of cancer chemotherapy are often more pronounced than its benefits. Regarding drugs used in cancer chemotherapy, their bioavailability and stability in the tumor microenvironment are the most important issues that need immediate addressing. Hence, an effective and reliable drug delivery system through which both rapid and precise targeting of treatment can be achieved is urgently needed. In this work, we discuss the development of various nanobased carriers in the advancement of cancer therapy—their properties, the potential of polymers for drug delivery, and recent advances in formulations. Additionally, we discuss the use of tumor metabolism-rewriting nanomedicines in strengthening antitumor immune responses and mRNA-based nanotherapeutics in inhibiting tumor progression. We also examine several issues, such as nanotoxicological studies, including their distribution, pharmacokinetics, and toxicology. Although significant attention is being given to nanotechnology, equal attention is needed in laboratories that produce nanomedicines so that they can record themselves in clinical trials. Furthermore, these medicines in clinical trials display overwhelming results with reduced side effects, as well as their ability to modify the dose of the drug.

This paper uses data from the 24 governorates in Tunisia over the period 2012–2020 to study the relationship between job insertion of higher education graduates into the formal labor market and a number of independent variables, namely active labor supply, labor demand, an active labor market policy program (named the CIVP program), and the waiting time for job insertion. The balanced panel, which includes 216 observations for each variable, was the basis of different tests and estimations. The results of the tests allowed the assessment of a fixed effects model and a long-term relationship using FMOLS and VECM models. Results show that, in the long term, active labor supply and the CIVP program have positive effects on the job insertion of higher education graduates. In contrast, the results in the short term do not appear significant, with a negative effect of the CIVP program that reflects the fact that companies exploit most of the benefits of this wage subsidy program on job insertion before final recruitment. Using the ARDL model, the individual results by governate show specific differences across areas.

Tuberculosis is a disease of poverty, discrimination, and socioeconomic burden. Epidemiological studies suggest that the mortality and incidence of tuberculosis are unacceptably higher worldwide. Genomic mutations in embCAB, embR, katG, inhA, ahpC, rpoB, pncA, rrs, rpsL, gyrA, gyrB, and ethR contribute to drug resistance reducing the susceptibility of Mycobacterium tuberculosis to many antibiotics. Additionally, treating tuberculosis with antibiotics also poses a serious risk of hepatotoxicity in the patient’s body. Emerging data on drug-induced liver injury showed that anti-tuberculosis drugs remarkably altered levels of hepatotoxicity biomarkers. The review is an attempt to explore the anti-mycobacterial potential of selected, commonly available, and well-known phytocompounds and extracts of medicinal plants against strains of Mycobacterium tuberculosis. Many studies have demonstrated that phytocompounds such as flavonoids, alkaloids, terpenoids, and phenolic compounds have antibacterial action against Mycobacterium species, inhibiting the bacteria's growth and replication, and sometimes, causing cell death. Phytocompounds act by disrupting bacterial cell walls and membranes, reducing enzyme activity, and interfering with essential metabolic processes. The combination of these processes reduces the overall survivability of the bacteria. Moreover, several phytochemicals have synergistic effects with antibiotics routinely used to treat TB, improving their efficacy and decreasing the risk of resistance development. Interestingly, phytocompounds have been presented to reduce isoniazid- and ethambutol-induced hepatotoxicity by reversing serum levels of AST, ALP, ALT, bilirubin, MDA, urea, creatinine, and albumin to their normal range, leading to attenuation of inflammation and hepatic necrosis. As a result, phytochemicals represent a promising field of research for the development of new TB medicines.

Contamination of water has been reported to be a serious environmental challenge. Therefore, development of novel technologies to tackle this issue is of fundamental importance from an environmental perspective. Nanocomposite membranes, which are utilized to improve the separation properties of standard polymeric membranes, have recently been of remarkable attention for purifying water from different contaminants including microorganisms, chemical compounds, dyes, etc. The principal aim of this review investigation is to present the current advancements towards the application of nanocomposite membranes in water treatment. Important pollutants in water sources are presented and their detrimental environmental impacts are discussed in detail. Furthermore, utilization of nanocomposite membranes in industrial activities such as desalination, nanoparticle separation, dye removal, antibacterial applications, inorganic pollutants separation and natural organic materials removal are presented and discussed in this paper. This review has also been organized to recommend better insights about different mechanisms of membrane separation and major existed pollutants in water sources, which their removal can provide better opportunities for global population to achieve sustainable and clean water.

In this study, a nano-drug delivery design based on (8, 8) carboxylated single-walled carbon nanotube (CNT-COOH) and folic acid (FA) decorated on CNT-COOH (CNT-FA) were investigated. These nanocarriers were applied to enhance therapeutic efficacy and reduce the adverse effects of the anticancer drug carboplatin (CBP) and the results were compared. The density functional theory (DFT) calculations were used to calculate the interactions between CNT-COOH, CNT-FA, and the CBP anticancer drug. The DFT computations were carried out by the DMol3 module using annealing and force field; universal in Material Studio 2017. The negative adsorption value of CBP by CNT-COOH and CNT-FA demonstrated that the physisorption configuration was stable and the drug-nanotube sidewall interaction was a spontaneous process. The current study investigated the adsorption strength and energy between the CBP molecule and CNT-COOH (8, 8) nanotubes with diameters of 12.160 Å and 11.674 Å and CNT-FA with diameters of 11.874 Å and 10.608 Å in the gas phase based on DFT calculations. The HOMO and LUMO energies of all compounds were obtained by the DMol3 module based on DFT-D. Also, sigma profile calculations (σ), energy gap (ΔEgap), and molecular electrostatic potentials (MEP) of CBP, CNT-COOH, CBP/CNT-COOH, CNT-FA, and CBP/CNT-FA were calculated. The results of ΔEgap confirmed the higher activity of the CBP/CNT-FA component (0.243 eV) compared to other structures. Molecular docking simulations between nano-carriers, including with or without CBP, and the crystal structure of human folate receptor alpha (FR, PDB ID: 4LRH), were performed. The results exhibited CNT-FA and CBP/CNT-FA were stronger on folate receptor compared with CNT-COOH and CBP/CNT-COOH, respectively.

Background: Globally Hepatitis C Virus (HCV) is considered to cause one of the major infection burdening public health. Presently HCV is categorized into seven genotypes and 67 subtypes, transmitted through various routes and vary in their pathogenesis. Aims and Objectives: Present work aimed to detect the prevalent HCV genotypes among individuals attending tertiary care hospital. Material and Methods: A hospital based cross sectional study was carried out. Patient blood samples received for screening of HCV antibodies were included in this study. Serum was subjected to Enzyme-Linked Immunosorbent Assay (ELISA) or Chemiluminescent Immunoassay (CLIA) and samples found to be positive for HCV antibodies were subjected to viral RNA extraction and genotyping. Results: Forty-two samples were found to be positive for HCV antibodies out of 19526 samples screened and were further subjected to genotyping. The genotypes identified were genotype-1, genotype-3, and genotype-4. Conclusion: Genotype-1 and genotype-3 predominate in this region. However, genotype-4 detection was novel to this region and has never been reported earlier. This study highlights the importance of screening HCV-positive patients for genotyping.

Immunotherapy, along with chemotherapy, targeted delivery, radiation and surgery has become one of the most common cancer treatments. The aim of cancer immunology is to use the bodys immune system to combat tumors and develop a robust antitumor immune response. In the last few years, immune checkpoint inhibitors and chimeric antigen receptor-modified T cells have made substantial advancements in cancer immunotherapy. By boosting cell type-specific delivery and immunological responses, nanocarriers like liposomes have the ability to enhance greater immune responses. The efficacy of anti-tumor therapeutics is being significantly improved as liposomes can assist in resolving a number of issues that can arise from a variety of cancer immunotherapies. Since, liposomes can be loaded with both hydrophilic and hydrophobic drugs and protect the immunotherapeutic agents loaded inside the core, they offer significant advantages over other nano delivery systems. The use of liposomes for accurate and timely delivery of immunotherapies to particular targeted neoplasms, with little or no injury to healthy cells, maximizes immunotherapy efficacy. Liposomes are also suitable vehicles for delivering medications simultaneously with other therapies such as chemotherapy, radiation, and phototherapy. Liposomal nanoparticles will be introduced and used as an objective immunotherapy delivery system for great precision, making them a viable cancer treatment approach.With an emphasis on dendritic cells, T cells, tumor and natural killer cells, and macrophages; outline of many forms of immune-therapies in oncology and cutting-edge advances in liposomal nanovesicles for cancer immunotherapy are covered in this review.

Preparation of small-molecule API (Active Pharmaceutical Ingredient) at submicron size would be of great benefit for pharmaceutical engineering, as the drug particles at submicron size possess higher solubility in water. Indeed, the drug bioavailability can be enhanced when the nanomedicine is prepared. In this study, the solubility of the drug desoxycorticosterone acetate (DA) is being examined to assess its viability of nanonization using supercritical operation. Two inputs are temperature and pressure which were considered for machine learning modeling in this study. The drug's solubility is the only output to be estimated by the optimized models. This dataset has 45 rows of data that were gathered at 5 different pressure and temperature levels. Support vector machine (SVM) is used as the core of the models built in this research. Epsilon-SVR and nu-SVR are models based on this concept, which together with two different polynomial and RBF kernels form the four models built in this research for estimation of DA drug solubility. The models are also optimized with the help of a new TLCO method. All four final models have an R2 score higher than 0.9, and among them, the Epsilon-SVR model with RBF kernel has the best performance with 0.967.

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood–brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.

Modeling and simulations based on machine learning techniques were conducted in this research for determination of pharmaceutical solubility in supercritical solvent for the sake of green processing development in the area of pharmaceutics. By this method, drug nanoparticles can be formed and controlled for better solubility and consequently bioavailability. We modeled the solubility of the drug namely desoxycorticosterone acetate (DA). The temperature and pressure are two inputs for the developed models, whereas the target output is the solubility of DA in the solvent. Indeed, models with two inputs and one output are developed in this study. This dataset contains 45 rows of data collected at five distinct temperatures and nine pressure levels. Three novel models are employed here including: HHO-MLP, HHO-RR, and HHO–KNN for theoretical determination of the drug solubility in the solvent. They are in fact MLP, Ridge Regression, and KNN models coupled with Harris Hawks optimizer (HHO) for hyper-parameter optimization. The HHO-MLP model has the best performance among models with R2 of 0.995, RMSE error rate of 0.194 and maximum error equal to 0.327. The model's findings can be used for estimation of the solubility data in wide range of T and P.

Production of solid-dosage drug nanoparticles was assessed by theoretical models to investigate the possibility of drug treatment via supercritical green processing. Nanonization can enhance drug solubility and consequently its bioavailability which is of great importance for pharmaceutical industry. This research presents a comparative study of three different regression models including Gaussian process regression, k-nearest neighbors, and multi-layer perceptron for predicting solvent density and solubility of Hyoscine drug. The models optimized using political optimizer (PO) algorithm. The results showed that all three optimized methods were able to predict density and solubility with high accuracy. PO-GPR achieved the highest R2 score for solubility (0.9984) and same for density (0.9999). The PO-MLP model achieved the high R2 score for density (0.9997) and the second-highest score for solubility (0.9945). PO-KNN also showed good performance for density (R2 = 0.9557) and solubility (R2 = 0.9783) but was outperformed by the other two models. In terms of RMSE and AARD%, PO-GPR and PO-MLP achieved lower error rates compared to PO-KNN. Overall, the results suggest that PO-GPR and PO-MLP are promising methods for predicting density and solubility of values. The models were useful for the application of drug nanonization and can be used to optimize the process.

The method of green technology which is based on supercritical solvent has been studied in this work for analysis of nanomedicine preparation of solid dosage oral medications. Given that the poor drug solubility in aqueous media is a big challenge in pharmaceutical industry, nanomedicines would help improve the drug solubility in aqueous media. The solubility of fludrocortisone acetate in supercritical carbon dioxide is modelled in this research using various machine learning methods because it is a crucial aspect of the expansion of the pharmaceutical business. For this purpose, the accessible data have two input features: a pressure range of 120–300 (bar) and a temperature range of 308–338 (K). MLP, v-SVR and MLR are the basic models used in this research, but not their raw versions. They are improved for modeling drug solubility and coupled with the grey wolf optimization (GWO) in order to optimize the models. The models optimized by GWO showed acceptable results, but among these models, MLP regression has shown better results when coupled with this optimization algorithm. This model has the RMSE error rate of 2.98 × 10−2 and its R2 score is 0.9797 in correlating the solubility data of the medicine.

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography–mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound’s structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 μg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

In recent years, N-Myristoyltransferase (NMT) has been identified as a new target for the treatment of fungal infections. It is observed that at present, there are increased rates of morbidity and mortality due to fungal infections. Hence, a series of novel myristic acid derivatives were designed via molecular docking studies and ADMET studies by targeting NMT (N-Myristoyltransferase). The designed myristic acid derivatives were synthesized by converting myristic acid into myristoyl chloride and coupling it with aryl amines to yield corresponding myristic acid derivatives. The compounds were purified and characterized via FTIR, NMR and HRMS spectral analyses. In this study, we carried out a target NMT inhibition assay. In the NMT screening assay results, the compounds 3u, 3m and 3t showed better inhibition compared to the other myristic acid derivatives. In an in vitro antifungal evaluation, the myristic acid derivatives were assessed against Candida albicans and Aspergillus niger strains by determining their minimal inhibitory concentrations (MIC50). The compounds 3u, 3k, 3r and 3t displayed superior antifungal capabilities against Candida albicans, and the compounds 3u, 3m and 3r displayed superior antifungal capabilities against Aspergillus niger compared to the standard drug FLZ (fluconazole). Altogether, we identified a new series of antifungal agents.

This work aimed to overcome the disadvantages of the oral administration of beta-caryophyllene and boost efficiency by developing a nanostructured lipid carrier for topical administration of the drug in skin disorders. The heat emulsification method was utilized to produce beta-caryophyllene-loaded nanostructured lipid carriers. The newly created formulation was examined for its particle size, entrapment efficiency, and zeta potential after being improved using the Box–Behnken Design. The chosen formulation underwent tests to determine its ex vivo skin retention, dermatokinetic, in vitro release, antioxidant, and confocal laser scanning microscopy study. The findings of the characterization of the nanostructured lipid carriers demonstrated that the particles had a spherical form and a size of 210.86 nm (0.263 polydispersity index). The entrapment efficiency was determined to be 86.74%, and the zeta potential was measured to be −26.97 mV. The in vitro release investigation showed that nanostructure lipid carriers were capable of releasing regulated amounts of beta-caryophyllene for up to 24 hrs. In comparison to the traditional gel formulation, the ex vivo investigation demonstrated a 1.94-fold increase in the skin’s capacity to retain the substance. According to the findings of the study, nanostructure lipid carriers loaded with beta-caryophyllene have the potential to be investigated for use as a topical administration method in skin disorders with enhanced skin retention and effectiveness.

Niosomes are multilamellar vesicles that effectively transfer active ingredients into the skin’s layers. To improve the active substance’s penetration across the skin, these carriers are frequently utilized as topical drug delivery systems. Essential oils (EOs) have garnered significant interest in the field of research and development owing to their various pharmacological activities, cost-effectiveness, and simple manufacturing techniques. However, these ingredients undergo degradation and oxidation over time, leading to a loss of functionality. Niosome formulations have been developed to deal with these challenges. The main goal of this work was to create a niosomal gel of carvacrol oil (CVC) to improve its penetration into the skin for anti-inflammatory actions and stability. By changing the ratio of drug, cholesterol and surfactant, various formulations of CVC niosomes were formulated using Box Behnken Design (BBD). A thin-film hydration technique using a rotary evaporator was employed for the development of niosomes. Following optimization, the CVC-loaded niosomes had shown: 180.23 nm, 0.265, −31.70 mV, and 90.61% of vesicle size, PDI, zeta potential, and EE%. An in vitro study on drug release discovered the rates of drug release for CVC-Ns and CVC suspension, which were found to be 70.24 ± 1.21 and 32.87 ± 1.03, respectively. The release of CVC from niosomes best fit the Higuchi model, and the Korsmeyer–Peppas model suggests that the release of the drug followed the non-Fickian diffusion. In a dermatokinetic investigation, niosome gel significantly increased CVC transport in the skin layers when compared to CVC–conventional formulation gel (CVC-CFG). Confocal laser scanning microscopy (CLSM) of rat skin exposed to the rhodamine B-loaded niosome formulation showed a deeper penetration of 25.0 µm compared to the hydroalcoholic rhodamine B solution (5.0 µm). Additionally, the CVC-N gel antioxidant activity was higher than that of free CVC. The formulation coded F4 was selected as the optimized formulation and then gelled with carbopol to improve its topical application. Niosomal gel underwent tests for pH determination, spreadability, texture analysis, and CLSM. Our findings imply that the niosomal gel formulations could represent a potential strategy for the topical delivery of CVC in the treatment of inflammatory disease.

Methyl anthranilate (MA) is a naturally derived compound commonly used in cosmetic products, such as skin care products, fine perfumes, etc. The goal of this research was to develop a UV-protective sunscreen gel using methyl-anthranilate-loaded silver nanoparticles (MA-AgNPs). The microwave approach was used to develop the MA-AgNPs, which were then optimized using Box–Behnken Design (BBD). Particle size (Y1) and absorbance (Y2) were chosen as the response variables, while AgNO3 (X1), methyl anthranilate concentration (X2), and microwave power (X3) were chosen as the independent variables. Additionally, the prepared AgNPs were approximated for investigations on in vitro active ingredient release, dermatokinetics, and confocal laser scanning microscopy (CLSM). The study’s findings showed that the optimal MA-loaded AgNPs formulation had a particle size, polydispersity index, zeta potential, and percentage entrapment efficiency (EE) of 200 nm, 0.296 mV, −25.34 mV, and 87.88%, respectively. The image from transmission electron microscopy (TEM) demonstrated the spherical shape of the nanoparticles. According to an in vitro investigation on active ingredient release, MA-AgNPs and MA suspension released the active ingredient at rates of 81.83% and 41.62%, respectively. The developed MA-AgNPs formulation was converted into a gel by using Carbopol 934 as a gelling agent. The spreadability and extrudability of MA-AgNPs gel were found to be 16.20 and 15.190, respectively, demonstrating that the gel may spread very easily across the skin’s surface. The MA-AgNPs formulation demonstrated improved antioxidant activity in comparison to pure MA. The MA-AgNPs sunscreen gel formulation displayed non-Newtonian pseudoplastic behaviour, which is typical of skin-care products, and was found to be stable during the stability studies. The sun protection factor (SPF) value of MA-AgNPG was found to be 35.75. In contrast to the hydroalcoholic Rhodamine B solution (5.0 µm), the CLSM of rat skin treated with the Rhodamine B-loaded AgNPs formulation showed a deeper penetration of 35.0 µm, indicating the AgNPs formulation was able to pass the barrier and reach the skin’s deeper layers for more efficient delivery of the active ingredient. This can help with skin conditions where deeper penetration is necessary for efficacy. Overall, the results indicated that the BBD-optimized MA-AgNPs provided some of the most important benefits over conventional MA formulations for the topical delivery of methyl anthranilate.

Nanotechnology is a rapidly developing field of research that studies materials having dimensions of less than 100 nanometers. It is applicable in many areas of life sciences and medicine including skin care and personal hygiene, as these materials are the essential components of various cosmetics and sunscreens. The aim of the present study was to synthesize Zinc oxide (ZnO) and Titanium dioxide (TiO2) nanoparticles (NPs) by using Calotropis procera (C. procera) leaf extract. Green synthesized NPs were characterized by UV spectroscopy, Fourier transform infrared (FTIR), X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM) to investigate their structure, size, and physical properties. The antibacterial and synergistic effects of ZnO and TiO2 NPs along with antibiotics were also observed against bacterial isolates. The antioxidant activity of synthesized NPs was analyzed by their α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging activity. In vivo toxic effects of the synthesized NPs were evaluated in albino mice at different doses (100, 200, and 300 mg/kg body weight) of ZnO and TiO2 NPs administered orally for 7, 14, and 21 days. The antibacterial results showed that the zone of inhibition (ZOI) was increased in a concentration-dependent manner. Among the bacterial strains, Staphylococcus aureus showed the highest ZOI, i.e., 17 and 14 mm against ZnO and TiO2 NPs, respectively, while Escherichia coli showed the lowest ZOI, i.e., 12 and 10 mm, respectively. Therefore, ZnO NPs are potent antibacterial agents compared to TiO2 NPs. Both NPs showed synergistic effects with antibiotics (ciprofloxacin and imipenem). Moreover, the DPPH activity showed that ZnO and TiO2 NPs have significantly (p > 0.05) higher antioxidant activity, i.e., 53% and 58.7%, respectively, which indicated that TiO2 has good antioxidant potential compared to ZnO NPs. However, the histological changes after exposure to different doses of ZnO and TiO2 NPs showed toxicity-related changes in the structure of the kidney compared to the control group. The current study provided valuable information about the antibacterial, antioxidant, and toxicity impacts of green synthesized ZnO and TiO2 NPs, which can be influential in the further study of their eco-toxicological effects.

The first conductive polymers (CPs) were developed during the 1970s as a unique class of organic substances with properties that are electrically and optically comparable to those of inorganic semiconductors and metals while also exhibiting the desirable traits of conventional polymers. CPs have become a subject of intensive research due to their exceptional qualities, such as high mechanical and optical properties, tunable electrical characteristics, ease of synthesis and fabrication, and higher environmental stability than traditional inorganic materials. Although conducting polymers have several limitations in their pure state, coupling with other materials helps overcome these drawbacks. Owing to the fact that various types of tissues are responsive to stimuli and electrical fields has made these smart biomaterials attractive for a range of medical and biological applications. For various applications, including the delivery of drugs, biosensors, biomedical implants, and tissue engineering, electrical CPs and composites have attracted significant interest in both research and industry. These bimodalities can be programmed to respond to both internal and external stimuli. Additionally, these smart biomaterials have the ability to deliver drugs in various concentrations and at an extensive range. This review briefly discusses the commonly used CPs, composites, and their synthesis processes. Further highlights the importance of these materials in drug delivery along with their applicability in various delivery systems.

Walnuts are one of the healthiest foods in the world because they are one of the best sources of beneficial nutrients, minerals, and antioxidants. They also contain key sources of energy. Despite several traditional uses, the leaves of Juglans regia L. have received little attention regarding phytochemical and pharmacological potential. Thus, the current study intended to find the walnut genotypes with the greatest antioxidant, anticancer, and antifungal activity. The total polyphenolic, flavonoid, and flavanol contents of leaves from 14 walnut genotypes were determined. Genotypes that accumulate flavonoid/flavonol contents (99.8–111.93 mg/g quercetin equivalent (QE) and 101.67–111.83 mg/g QE) showed significantly higher ferric reducing antioxidant potential (FRAP) activity (128.2–148.1 μM Fe2+/g dry weight (DW)] than other genotypes. Maximum divergence in the quercetin content (0.8–1.23 mg/g) of walnut genotypes was obtained by cluster analysis. The active component, quercetin, was measured using RP-HPLC. Moreover, the extracts were investigated for antifungal and anticancer assays. We report the significant antifungal potential of walnut leaf genotypes against Candida glabrata, Candida albicans, and Candida tropicalis, with 57.7–93.6%, 26.8–51.5%, and 26.8–51.5% inhibition, respectively. The most significant antiproliferative effect was shown by Opex Culchry, which exhibited 9.4% cell viability at a concentration of 25 µL (0.75 mg) against lung (A549) cell lines. Chenovo exhibited 2.9, 6.2, and 2.2% cell viability, Opex Culchry exhibited 2, 1.5, and 2.4% cell viability, and Sulieman showed 7.6, 0.9, and 7% cell viability against the colon (HCT116) cell lines. The results showed that walnut leaves possess enormous potential as antioxidants, and as anticancer and antifungal agents.

The death rate from breast cancer (BC) has dropped due to early detection and sophisticated therapeutic options, yet drug resistance and relapse remain barriers to effective, systematic treatment. Multiple mechanisms underlying miRNAs appear crucial in practically every aspect of cancer progression, including carcinogenesis, metastasis, and drug resistance, as evidenced by the elucidation of drug resistance. Non-coding RNAs called microRNAs (miRNAs) attach to complementary messenger RNAs and degrade them to inhibit the expression and translation to proteins. Evidence suggests that miRNAs play a vital role in developing numerous diseases, including cancer. They affect genes critical for cellular differentiation, proliferation, apoptosis, and metabolism. Recently studies have demonstrated that miRNAs serve as valuable biomarkers for BC. The contrast in the expression of miRNAs in normal tissue cells and tumors suggest that miRNAs are involved in breast cancer. The important aspect behind cancer etiology is the deregulation of miRNAs that can specifically influence cellular physiology. The main objective of this review is to emphasize the role and therapeutic capacity of tumor suppressor miRNAs in BC and the advancement in the delivery system that can deliver miRNAs specifically to cancerous cells. Various approaches are used to deliver these miRNAs to the cancer cells with the help of carrier molecules, like nanoparticles, poly D, L-lactic-co-glycolic acid (PLGA) particles, PEI polymers, modified extracellular vesicles, dendrimers, and liposomes. Additionally, we discuss advanced strategies of TS miRNA delivery techniques such as viral delivery, self-assembled RNA-triple-helix hydrogel drug delivery systems, and hyaluronic acid/protamine sulfate inter-polyelectrolyte complexes. Subsequently, we discuss challenges and prospects on TS miRNA therapeutic delivery in BC management so that miRNAs will become a routine technique in developing individualized patient profiles.

CDK4/6 and aromatase are prominent targets for breast cancer drug discovery and are involved in abnormal cell proliferation and growth. Although aromatase inhibitors have proven to be effective (for example exemestane, anastrozole, letrozole), resistance to treatment eventually occurs through the activation of alternative signaling pathways, thus evading the antiproliferative effects of aromatase inhibitors. One of the evasion pathways is Cylin D-CDK4/6-Rb signaling that promotes tumor proliferation and resistance to aromatase inhibitors. There is significant evidence that the sequential inhibition of both proteins provides therapeutic benefits over the inhibition of one target. The basis of this study objective is the identification of molecules that are likely to inhibit both CDK4/6 and aromatase by computational chemistry techniques, which need further biochemical studies to confirm. Initially, a structure-based pharmacophore model was constructed for each target to screen the sc-PDB database. Consequently, pharmacophore screening and molecular docking were performed to evaluate the potential lead candidates that effectively mapped both of the target pharmacophore models. Considering abemaciclib (CDK4/6 inhibitor) and exemestane (aromatase inhibitor) as reference drugs, four potential virtual hit candidates (1, 2, 3, and 4) were selected based on their fit values and binding interaction after screening a sc-PDB database. Further, molecular dynamics simulation studies solidify the stability of the lead candidate complexes. In addition, ADMET and DFT calculations bolster the lead candidates. Hence, these combined computational approaches will provide a better therapeutic potential for developing CDK4/6-aromatase dual inhibitors for HR+ breast cancer therapy.

The aim of this research work was to formulate and evaluate ciprofloxacin hydrochloride-loaded nanocarriers for treating dental infections and bone regeneration. Periodontal infection is associated with inflammation, soft tissue destruction, and bone loss. The objective of the study was to extract β tricalcium phosphate (β-TCP) from coral beach sand using the hydrothermal conversion method and load these nanocarriers with ciprofloxacin hydrochloride. The developed drug-loaded nanocarriers were evaluated for various parameters. In vitro drug-loading studies showed the highest drug loading of 71% for F1 with a drug: carrier ratio compared to plain ciprofloxacin hydrochloride gel. β-TCP and nanocarriers were evaluated for powder characteristics and the results were found to have excellent and fair flowability. In vitro drug release studies conducted over a period of 5 days confirmed the percentage drug release of 96% at the end of 120 h. Nanocarriers were found to be effective against S. aureus and E. coli showing statistically significant antibacterial activity at (* p < 0.05) significant level as compared to plain ciprofloxacin hydrochloride gel. The particle size of β-TCP and nanocarriers was found to be 2 µm. Fourier transform infra-red studies showed good compatibility between the drug and the excipients. Differential scanning calorimetry studies revealed the amorphous nature of the nanocarriers as evident from the peak shift. It is obvious from the XRD studies that the phase intensity was reduced, which demonstrates a decrease in crystallinity. Nanocarriers released the drug in a controlled manner, hence may prove to be a better option to treat dental caries as compared to conventional treatments.

Celecoxib (CLB) is a highly hydrophobic selective cyclo-oxygenase inhibitor with high plasma protein binding and undergoes extensive hepatic metabolism. CLB is highly effective in the treatment of osteo and rheumatoid arthritis as first line therapy but produces severe gastro-intestinal toxicities and cardiovascular side effects. In this research, stealth liposomes of CLB were developed with the intention to reduce the side effects and increase the accumulation of drug in the sites of inflammation. Stealth liposomes were prepared by thin film hydration technique using distearoylphosphatidylcholine and PE-PEG 2000 with variable amounts of cholesterol and characterized. The effects of various lipids such as hydrogenated soy phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoylphosphatidylcholine and cholesterol content on % drug encapsulation was investigated. The optimized stealth liposomes were characterized by FT-IR and DSC for possible drug excipients interaction. Pharmacokinetics, pharmacodynamics and biodistribution studies were carried out for the stealth liposomes. The results revealed that the stealth liposomes reduced the inflammation to the larger magnitude and have also sustained the magnitude when compared to free drug along with maximum analgesic response. Higher elimination half-life, AUC, MRT and lowered clearance rate denotes the extended bioavailability of the drug in blood. Biodistribution studies revealed that stealth liposomes extend the circulation time of liposomes in blood by decreasing opsonisation and be less concentrated in kidney, thereby reducing the toxicities to RES and renal organs and facilitate the drug accumulation in the area of inflammation. Our results indicated that CLB, without the requirement of modifications to enhance solubilisation, can be encapsulated and released from liposomal formulations. This new-fangled drug delivery approach may be used to circumvent the low bioavailability and toxic side effects of oral CLB formulations.

Complications of urinary tract infections (UTIs) like kidney failure and septicaemia develop once infections spread from the upper urinary tract to other parts of the body by haematogenous dissemination and they pose great health and economic burden to the countries. This retrospective study was conducted among 132 patients with bacterial UTIs in the inpatient department of tertiary care hospital in Abha, Saudi Arabia. During the study period, Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia) along with other 15 different bacteria were isolated. A significant difference (P < 0.05) was observed between the male and female children population in different age groups. We observed fever (84.09%) as a major symptom (P < 0.05), and seizure (9%) was reported as a major concomitant condition among UTI cases. Around 31.82% of E. coli was found to be the most common uropathogens in pediatric cases followed by 25% in K. pneumoniae. E. coli was observed to be more susceptible (92.86%) to amikacin, ceftriaxone, levofloxacin, ertapenem, gentamycin, meropenem, piperacillin-tazobactam, tigecycline, and ceftazidime. However, meropenem, tigecycline, and amikacin were observed to be effective in 100% of cases of K. pneumoniae. Meanwhile, cephalosporins were the most commonly prescribed drug category among different classes of drugs. Almost 99% of pediatric cases, based on their age, were admitted to the ward, and drugs were administered intravenously. We concluded that microbiology laboratory evidence on the causative organisms and choice of treatment together allows tailoring appropriate treatment regimens in conjunction with clinical experiences.

Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds’ immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.

Immunotherapy shows a lot of promise for addressing the problems with traditional cancer treatments. Researchers and clinicians are working to create innovative immunological techniques for cancer detection and treatment that are more selective and have lower toxicity. An emerging field in cancer therapy, immunomodulation offers patients an alternate approach to treating cancer. These therapies use the host’s natural defensive systems to identify and remove malignant cells in a targeted manner. Cancer treatment is now undergoing somewhat of a revolution due to recent developments in nanotechnology. Diverse nanomaterials (NMs) have been employed to overcome the limits of conventional anti-cancer treatments such as cytotoxic, surgery, radiation, and chemotherapy. Aside from that, NMs could interact with live cells and influence immune responses. In contrast, unexpected adverse effects such as necrosis, hypersensitivity, and inflammation might result from the immune system (IS)’s interaction with NMs. Therefore, to ensure the efficacy of immunomodulatory nanomaterials, it is essential to have a comprehensive understanding of the intricate interplay that exists between the IS and NMs. This review intends to present an overview of the current achievements, challenges, and improvements in using immunomodulatory nanomaterials (iNMs) for cancer therapy, with an emphasis on elucidating the mechanisms involved in the interaction between NMs and the immune system of the host.

Antimicrobial resistance is a major global health concern and one of the gravest challenges to humanity today. Antibiotic resistance has been acquired by certain bacterial strains. As a result, new antibacterial drugs are urgently required to combat resistant microorganisms. Species of Trichoderma are known to produce a wide range of enzymes and secondary metabolites that can be exploited for the synthesis of nanoparticles. In the present study, Trichoderma asperellum was isolated from rhizosphere soil and used for the biosynthesis of ZnO NPs. To examine the antibacterial activity of ZnO NPs against human pathogens, Escherichia coli and Staphylococcus aureus were used. The obtained antibacterial results show that the biosynthesized ZnO NPs were efficient antibacterial agents against the pathogens E. coli and S. aureus, with an inhibition zone of 3–9 mm. The ZnO NPs were also effective in the prevention of S. aureus biofilm formation and adherence. The current work shows that the MIC dosages of ZnO NPs (25, 50, and 75 μg/mL) have effective antibacterial activity and antibiofilm action against S. aureus. As a result, ZnO NPs can be used as a part of combination therapy for drug-resistant S. aureus infections, where biofilm development is critical for disease progression.

The novel pathogenic virus was discovered in Wuhan, China (December 2019), and quickly spread throughout the world. Further analysis revealed that the pathogenic strain of virus was corona but it was distinct from other coronavirus strains, and thus it was renamed 2019-nCoV or SARS-CoV-2. This coronavirus shares many characteristics with other coronaviruses, including SARS-CoV and MERS-CoV. The clinical manifestations raised in the form of a cytokine storm trigger a complicated spectrum of pathophysiological changes that include cardiovascular, kidney, and liver problems. The lack of an effective treatment strategy has imposed a health and socio-economic burden. Even though the mortality rate of patients with this disease is lower, since it is judged to be the most contagious, it is considered more lethal. Globally, the researchers are continuously engaged to develop and identify possible preventive and therapeutic regimens for the management of disease. Notably, to combat SARS-CoV-2, various vaccine types have been developed and are currently being tested in clinical trials; these have also been used as a health emergency during a pandemic. Despite this, many old antiviral and other drugs (such as chloroquine/hydroxychloroquine, corticosteroids, and so on) are still used in various countries as emergency medicine. Plant-based products have been reported to be safe as alternative options for several infectious and non-infectious diseases, as many of them showed chemopreventive and chemotherapeutic effects in the case of tuberculosis, cancer, malaria, diabetes, cardiac problems, and others. Therefore, plant-derived products may play crucial roles in improving health for a variety of ailments by providing a variety of effective cures. Due to current therapeutic repurposing efforts against this newly discovered virus, we attempted to outline many plant-based compounds in this review to aid in the fight against SARS-CoV-2.

Aggregation of Amyloid-β (Aβ) leads to the formation and deposition of neurofibrillary tangles and plaques which is the main pathological hallmark of Alzheimer’s disease (AD). The bioavailability of the drugs and their capability to cross the BBB plays a crucial role in the therapeutics of AD. The present study evaluates the Memantine Hydrochloride (MeHCl) and Tramiprosate (TMPS) loaded solid lipid nanoparticles (SLNs) for the clearance of Aβ on SHSY5Y cells in rat hippocampus. Molecular docking and in vitro Aβ fibrillation were used to ensure the binding of drugs to Aβ. The in vitro cell viability study showed that the M + T SLNs showed enhanced neuroprotection against SHSY5Y cells than the pure drugs (M + T PD) in presence of Aβ (80.35µM ± 0.455 µM) at a 3:1 molar ratio. The Box–Behnken Design (BBD) was employed to optimize the SLNs and the optimized M + T SLNs were further characterized by %drug entrapment efficiency (99.24 ± 3.24 of MeHCl and 89.99 ± 0.95 of TMPS), particle size (159.9 ± 0.569 nm), PDI (0.149 ± 0.08), Zeta potential (−6.4 ± 0.948 mV), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM) and in vitro drug release. The TEM & AFM analysis showed irregularly spherical morphology. In vitro release of SLNs was noted up to 48 h; whereas the pure drugs released completely within 3 hrs. M + T SLNs revealed an improved pharmacokinetic profile and a 4-fold increase in drug concentration in the brain when compared to the pure drug. Behavioral tests showed enhanced spatial memory and histological studies confirmed reduced Aβ plaques in rat hippocampus. Furthermore, the levels of Aβ decreased in AlCl3-induced AD. Thus, all these noted results established that the M + T SLNs provide enhanced neuroprotective effects when compared to pure and individual drugs and can be a promising therapeutic strategy for the management of AD.

The current study was designed to investigate the feasibility of incorporating the water-insoluble lipophilic drug Alprazolam (Alp) into solid lipid nanoparticles (SLNs) to offer the combined benefits of the quick onset of action along with the sustained release of the drug. Therefore, compritol-based alprazolam-loaded SLNs (Alp-SLNs) would provide early relief from anxiety and sleep disturbances and long-lasting control of symptoms in patients with depression, thereby enhancing patient compliance. The optimized Alp-SLNs analyzed by DLS and SEM showed consistent particle size of 92.9 nm with PI values and standard deviation of the measurements calculated at

Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine because it is well-conserved and plays a vital role in viral replication. Mpro inhibition can stop the replication, transcription as well as recombination of SARS-CoV-2 after the infection and thus can halt the formation of virus particles, making Mpro a viable therapeutic target. Here, we constructed a phytochemical dataset based on a rigorous literature review and explored the probability that various phytochemicals will bind with the main protease using a molecular docking approach. The top three hit compounds, medicagol, faradiol, and flavanthrin, had binding scores of −8.3, −8.6, and −8.8 kcal/mol, respectively, in the docking analysis. These three compounds bind to the active groove, consisting of His41, Cys45, Met165, Met49, Gln189, Thr24, and Thr190, resulting in main protease inhibition. Moreover, the multiple descriptors from the molecular dynamics simulation, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond analysis, confirmed the stable nature of the docked complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed a lack of toxicity or carcinogenicity for the screened compounds. Our computational analysis may contribute toward the design of an effective drug against the main protease of SARS-CoV-2.

Background and Introduction: Saxagliptin is a hypoglycemic drug that acts as a dipeptidyl peptidase-4 (DPP-4) inhibitor and is preferably used in the treatment of Type 2 Diabetes Mellitus (T2DM). It is safe and tolerable; however, the major disadvantage associated with it is its low bioavailability. Aim: The present research aimed to enhance the bioavailability of the drug by enteric coating with a polymer that controls the rate of drug delivery, and it was prepared as Solid Lipid Nanoparticles (SLNs). Methodology: In the current study, various SLN formulations were developed using a central composite design (CCD) module using Design Expert-11 software. A modified solvent injection technique was used to prepare Saxagliptin nanoparticles coated with Eudragit RS100. The CCD was used to determine the independent variables and their effect on dependent variables at varied levels. Evaluation studies such as particle size analysis, Zeta potential, polydispersity index (PDI), drug loading, entrapment efficiency, in-vitro drug release studies, and in vivo pharmacokinetic studies were performed for the optimized SLN formulation. The reversed-phase HPLC method was developed and validated for the estimation of the pharmacokinetic parameters of the pure drug and prepared SLNs. Results: The effect of independent variables (A1: amount of lipid, A2: amount of polymer, A3: surfactant concentration, and A4: homogenization speed) on dependent variables (R1: particle size, and R2: entrapment efficiency) was established in great detail. Observed responses of the prepared and optimized Saxagliptin SLN were close to the predicted values by the CCD. The prepared SLNs depicted particle sizes in the range of 212–442 nm. The particle size analysis results showed that an increase in the lipid concentration led to an increase in particle size. The developed bioanalytical method was noted to be very specific and robust. The method accuracy varied from 99.16% to 101.95% for intraday, and 96.08% to 103.12% for inter day operation at low (5 mcg/mL), moderate (10 mcg/mL), and higher (15 mcg/mL) drug concentrations. The observed Zeta potential values for the prepared SLNs were in the range of −41.09 ± 0.11 to 30.86 ± 0.63 mV suggesting quite good stability of the SLNs without any aggregation. Moreover, the polydispersity indices were in the range of 0.26 ± 0.051 to 0.45 ± 0.017, indicative of uniformity of sizes among the prepared SLNs. In vivo study outcomes proved that Saxagliptin oral bioavailability significantly enhanced in male Albino Wistar Rats via SLN formulation and Eudragit RS100 coating approach. Conclusions: The developed and optimized Saxagliptin SLNs revealed enhanced Saxagliptin bioavailability in comparison to the native drug. Thus, this formulation strategy can be of great importance and can be implied as a promising approach to enhance the Saxagliptin bioavailability for facilitated T2DM therapy.

Staphylococcus lugdunensis is a coagulase-negative, Gram-positive, and human pathogenic bacteria. S. lugdunensis is the causative agent of diseases, such as native and prosthetic valve endocarditis, meningitis, septic arthritis, skin abscesses, brain abscess, breast abscesses, spondylodiscitis, post-surgical wound infections, bacteremia, and peritonitis. S. lugdunensis displays resistance to beta-lactam antibiotics due to the production of beta-lactamases. This study aimed to identify potential novel essential, human non-homologous, and non-gut flora drug targets in the S. lugdunensis strain N920143, and to evaluate the potential inhibitors of drug targets. The method was concerned with a homology search between the host and the pathogen proteome. Various tools, including the DEG (database of essential genes) for the essentiality of proteins, the KEGG for pathways analysis, CELLO V.2.5 for cellular localization prediction, and the drug bank database for predicting the druggability potential of proteins, were used. Furthermore, a similarity search with gut flora proteins was performed. A DNA-binding response-regulator protein was identified as a novel drug target against the N920143 strain of S. lugdunensis. The three-dimensional structure of the drug target was modelled and validated with the help of online tools. Furthermore, ten thousand drug-like compounds were retrieved from the ZINC15 database. The molecular docking approach for the DNA-binding response-regulator protein identified ZINC000020192004 and ZINC000020530348 as the most favorable compounds to interact with the active site residues of the drug target. These two compounds were subjected to an MD simulation study. Our analysis revealed that the identified compounds revealed more stable behavior when bound to the drug target DNA-binding response-regulator protein than the apostate.

Quercetin (Qu) is a natural flavonoid present in many commonly consumed food items and is also identified as a potential anticancer agent. The present study evaluates the Qu-loaded polymeric mixed micelles (Qu-PMMs) against C6 and U87MG glioma cell lines. The Box–Behnken Design (BBD) was employed to study the influence of independent variables such as Soluplus, Vitamin-E polyethyleneglycol-1000 succinate (E-TPGS), and poloxamer 407 concentrations on dependent variables including particle size (PS), polydispersity index (PDI), and percentage entrapment efficiency (%EE) of the prepared Qu-PMMs. The Qu-PMMs were further characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), and were assessed for in vitro drug release, effect on cell viability, migration, cellular uptake, and apoptosis assays. The PS, PDI, and % EE of the optimized PMMs were 107.16 ± 1.06 nm, 0.236 ± 0.053, and 77.46 ± 1.94%, respectively. The FTIR and XRD revealed that the Qu was completely entrapped inside the PMMs. The SEM analysis confirmed the spherical shape of micelles. The in vitro cell viability study showed that the Qu-PMMs had 1.7 times higher cytotoxicity against C6 and U87MG cells than Qu pure drug (Qu-PD). Furthermore, Qu-PMMs demonstrated superior cellular uptake, inhibited migration, and induced apoptosis when tested against C6 and U87MG cells than pure Qu. Thus, the polymeric mixed micelle (PMMs) enhanced the therapeutic effect of Qu and can be considered an effective therapeutic strategy to treat Glioma.

Cancer has long been regarded as one of the world’s most fatal diseases, claiming the lives of countless individuals each year. Stomach cancer is a prevalent cancer that has recently reached a high number of fatalities. It continues to be one of the most fatal cancer forms, requiring immediate attention due to its low overall survival rate. Early detection and appropriate therapy are, perhaps, of the most difficult challenges in the fight against stomach cancer. We focused on positive tactics for stomach cancer therapy in this paper, and we went over the most current advancements and progressions of nanotechnology-based systems in modern drug delivery and therapies in great detail. Recent therapeutic tactics used in nanotechnology-based delivery of drugs aim to improve cellular absorption, pharmacokinetics, and anticancer drug efficacy, allowing for more precise targeting of specific agents for effective stomach cancer treatment. The current review also provides information on ongoing research aimed at improving the curative effectiveness of existing anti-stomach cancer medicines. All these crucial matters discussed under one overarching title will be extremely useful to readers who are working on developing multi-functional nano-constructs for improved diagnosis and treatment of stomach cancer.

The goal of present investigation was to formulate and evaluate ketorolac tromethamine (KTM) mucoadhesive buccal films. The films were prepared by solvent evaporation method using PVP K30, HPMC K4M, HPMC K15M, carbopol 934, chitosan, and sodium alginate as polymers and propylene glycol as plasticizer. The films were evaluated for thickness, weight variation, folding endurance, surface pH, swelling index, in vitro residence time, in vitro diffusion, release kinetics, ex vivo permeation, in vitro-ex vivo correlation, and in vivo pharmacological activities such as anti-inflammatory and analgesic activity. Thickness, weight, drug content, and folding endurance were found to be uniform for the films. Surface pH was 6.85±0.10, and swelling index was the highest (27.27±0.37) for the best film containing carbopol 934 along with sodium alginate and PVP K 30 (formulation code F2). In vitro residence time was greater than 5 h, and in vitro % drug release was 98.71% for F2. It exhibited 55.49% of swelling inhibition at 5 h, and above 38.88% was maintained at even 8 h. The film F2 has shown maximum analgesic response of 17 sec at 5 h, and the response of 11 sec was maintained at even 8 h. The anti-inflammatory and analgesic effect of F2 was found be maximum while sustaining the effect for prolonged period when compared to free drug solution. Thus, KTM mucoadhesive buccal film containing carbopol 934, sodium alginate, and PVP K30 could be an effective alternative for conventional therapy with improved efficacy.

Aim. The study is aimed at developing curcumin suppositories as a promising approach for natural antifungal management of vaginal candidiasis in cervical cancer patients to eradicate side effects produced by current antifungal drugs. The objective of the study was to optimize the suppositories using optimal (custom) design employing Design-Expert 13 software to recognize the concentration of polyethylene glycols (PEG) and Poloxamer 407 and obtain a stable suppository. Methodology. Combinations of PEG 1500 (10%–40%), PEG 6000 (40%–60%), and Poloxamer 407 (5%–30%) were entered as factors, and the responses evaluated were hardness, deformation time, and % drug release. In addition, the formulation was also evaluated for visual examination, weight variation, pH determination, drug content, hardness test, disintegration time, melting zone, deformation time, in vitro drug release, antifungal activity, and stability tests. Results. Suppositories were devoid of holes and cracks, with a characteristic odor and a dark yellowish-orange color. All formulations passed the weight variation test. Formulations exhibited pH ranging from 5.5 to 6.5. Drug content was observed to be 98.65±0.041%–99.85±0.041%. The hardness of the formulation was between 2.9 and 4.2 kg/cm2. The disintegration time ranged from 11±0.052 min to 20±0.011 min. The melting point was between 41±0.31°C and 58±0.62°C. Deformation time ranged from 10±0.45 to 35±0.52 min. Most of the formulations resulted in 90% of drug release at 40 min, and the zone of inhibition noted was 19.6±0.4 mm. All the selected factors have a significant effect on the response chosen for the study. Conclusion. The optimized curcumin vaginal suppository formulation can be an efficient herbal treatment devoid of side effects to treat vaginal candidiasis in cervical cancer patients.

The purpose of the research was to optimize the preparation of duloxetine hydrochloride (duloxetine HCl) delayed release tablets. Duloxetine HCl produces a toxic substance called alpha-naphthol when duloxetine HCl is in contact with gastric fluid. Thus, duloxetine HCl when given orally needed a protective enteric coating that disable the delivery of duloxetine HCl in gastric fluid while enabling the drug delivery only in small intestine. Four different core tablets were prepared by direct compression technique, and the one which displayed quick disintegration and dissolution was chosen for enteric coating. The compressed tablets were enteric coated by dip coating technique. Since subcoating is required to safeguard the enteric coating, the core tablets were subcoated by using polymer HPMC K15M and then enteric coated with Eudragit L 100. The prepared tablets were assessed for the entire precompression and postcompression characteristics. FTIR study revealed the existence of all prominent peaks signifying its compatibility and authenticity. The in vitro studies showed that enteric-coated tablets were capable of restricting release in acidic media. The formulation F8 was optimised with 5% and 15% increase in weight of seal coat and enteric coat with good dissolution profile. Stability studies revealed that the optimized formulation was intact without any deterioration for 3 months. In conclusion, the optimized formulation could resist the drug release in acidic environment of gastrointestinal region and release the drug at a time once the tablet reaches the intestine.

Cancer is a group of disorders characterized by uncontrolled cell growth that affects around 11 million people each year globally. Nanocarrier-based systems are extensively used in cancer imaging, diagnostics as well as therapeutics; owing to their promising features and potential to augment therapeutic efficacy. The focal point of research remains to develop new-fangled smart nanocarriers that can selectively respond to cancer-specific conditions and deliver medications to target cells efficiently. Nanocarriers deliver loaded therapeutic cargos to the tumour site either in a passive or active mode, with the least drug elimination from the drug delivery systems. This review chiefly focuses on current advances allied to smart nanocarriers such as dendrimers, liposomes, mesoporous silica nanoparticles, quantum dots, micelles, superparamagnetic iron-oxide nanoparticles, gold nanoparticles and carbon nanotubes, to list a few. Exhaustive discussion on crucial topics like drug targeting, surface decorated smart-nanocarriers and stimuli-responsive cancer nanotherapeutics responding to temperature, enzyme, pH and redox stimuli have been covered.

Tamarix aphylla is a well-known species of the genus Tamarix. T. aphylla (Tamaricaceae) is a perennial tree in Asia, the Middle East, and Central Africa. It is used as a carminative diuretic in tuberculosis, leprosy, and hepatitis. Various pharmacological properties have been shown by T. aphylla, such as antidiabetic, anti-inflammatory, antibacterial, antifungal, anticholinesterase, and wound-healing activity. However, T. aphylla has not received much attention for its secondary metabolites and bioactive constituents. Research has shown that this plant has hidden potential that needs to be explored. This review aims to cover botanical classification, geographical distribution, taxonomy, ethnobotanical uses, and the phytochemical compounds found in T. aphylla. The toxicology and pharmacological effects of T. aphylla are also discussed. We examined various scholarly resources to gather information on T. aphylla, including Google Scholar, Scopus, Science Direct, Springer Link, PubMed, and Web of Science. The finding of this work validates a connection between T. aphylla in conventional medicine and its antidiabetic, antibacterial, anti-inflammatory, wound-healing, antifungal, anticholinesterase, and other biological effects. T. aphylla’s entire plant (such as bark, leaves, fruits) and root extracts have been used to treat hypertension, stomach discomfort, hair loss, cough and asthma, abscesses, wounds, rheumatism, jaundice, fever, tuberculosis, and gum and tooth infection. The phytochemical screening revealed that noticeably all extracts were devoid of alkaloids, followed by the presence of tannins. In addition, different parts have revealed the existence of steroids, flavonoids, cardiac glycosides, and byproducts of gallic acid and ellagic acid. T. aphylla has shown many valuable activities against different diseases and supports its traditional uses. Therefore, high-quality preclinical research and well-designated clinical trials are needed to establish the efficacy and safety of this plant in humans.