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The issue of drug resistance and tolerance presents a significant challenge as it diminishes the efficacy and potency of medications, posing a formidable obstacle for physicians striving to enhance pharmacological therapy worldwide. These resistance mechanisms can arise from genetic predispositions or as a consequence of medical interventions. Notably, acquired resistance or tolerance may extend to other drugs within the same or different classes, despite differing mechanisms of action. This phenomenon leads to the ineffectiveness of various pharmacological treatments over time, hindering the attainment of complete remission for numerous illnesses spanning metabolic disorders, autoimmune diseases, carcinomas, infectious diseases, cardiovascular diseases, and neurological disorders. Vitamin D, an essential lipid‐soluble nutrient crucial for regulating calcium and phosphorus levels, is emerging as a potential solution to counteract treatment resistance and tolerance in various conditions such as cancer, tuberculosis, and depression. This review scrutinizes existing research and offers insights for future investigations aimed at fully elucidating the therapeutic potential of vitamin D in mitigating the challenges associated with prolonged medication regimens and drug treatment failures. Trial Registration: ClinicalTrials.gov identifier: NCT01169259 and NCT04342598. [ABSTRACT FROM AUTHOR]

Drug discovery is the process by which new drug candidates are discovered and drug development takes place. To enhance the efficiency, accuracy, and speed of the drug discovery process, machine learning (ML) could play a transformative role. For this research study, antidiabetic natural compounds from C. intybus, which is commonly known as chicory, were selected, as they have promising antidiabetic properties that can complement conventional diabetes treatments. A bioactive natural compound dataset was retrieved on the chicory plant using Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) public source information. This collected dataset was analyzed for its absorption, distribution, metabolism, and excretion (ADME) properties using the SwissADME online tool. Principal component analysis (PCA) and correlation analysis were performed using trial-version XLSTAT software 2014.5.03 and Python. The obtained dataset from SwissADME was subjected to cleaning, after that, it was used to develop machine learning models, such as support vacuum (SVM) ML, random forest (RF), Naive Bayes (NB), and decision tree (DT). The Lipinski rule of violation was chosen as the target variable. To improve the vitality of the created ADME dataset, PCA, a biplot graph, and correlation analysis were carried out. A large dataset of naturally occurring antidiabetic compounds was used to predict the drug-likeness of ML models that were effectively deployed on heterogeneous ADME datasets. Among all these ML models, DT performed better than the rest of the models. [ABSTRACT FROM AUTHOR]

The current work aims to develop a bigel-containing clobetasol propionate-loaded PLGA microparticles and further assess its in vitro, ex vivo, and in vivo behavior for psoriasis management. PLGA microparticles (2%w/w) containing clobetasol propionate were developed by solvent evaporation technique. For the developed particles, size, drug loading, entrapment efficiency, and surface morphology were determined. Further, the particles were suspended into bigel developed from oleogel and hydrogel (40:60) and assessed for stability, in vitro drug release, ex vivo skin permeation, retention, and in vivo study in BALB c mice for antipsoriatic potential. PLGA microparticles developed by solvent evaporation were found to have a mean particle size of 19.45 ± 1.74 μm. Drug loading and entrapment efficiency for clobetasol were found to be 43.5 ± 4.94% and 94.5 ± 3.68%, respectively. For the developed bigel, sustained in vitro drug release was observed till 7 h. Ex vivo skin permeation with the developed formulation was found to be higher than the marketed formulation and drug suspended in bigel. A retention study performed on pig skin suggested the topical skin retention of the drug. Further, the psoriatic model was developed in BALB c mice with IMQ cream, and it was observed that the developed formulation helped considerably reduce the irritation score and PASI scoring in mice as compared to the standard treatment. The same is corroborated with the help of histopathological studies performed by Hematoxylin and Eosin (H&E) staining in the same animals. The study findings suggest that clobetasol microparticle-loaded bigel formulation appeared to be a promising therapy option for psoriasis. [ABSTRACT FROM AUTHOR]

This study investigates whether Andrographolide-loaded Lactose β-Cyclodextrin (ALN-βCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to β-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the nanoparticles, which were characterised for particle size, PDI, zeta potential, and drug release. The nanoparticles exhibited a size of 247.9 ± 3.2 nm, a PDI of 0.5 ± 0.02, and a zeta potential of 26.8 ± 2.5 mV. FTIR and TEM analyses, along with in vitro drug release and BBB permeability studies, confirmed their stability and efficacy. Behavioural tests, including the Elevated Plus Maze, Y-Maze, Object Recognition, and Locomotor Activity tests, demonstrated significant improvements in memory, motor coordination, and exploration time in the nanoparticle-treated groups. The group treated with ALN-βCD at a dose of 100 mg/kg/p.o. showed superior cognitive performance compared to the group receiving free andrographolides (AG). Biochemical assays indicated a significant reduction in acetylcholinesterase activity and lipid peroxidation, suggesting increased acetylcholine levels and reduced oxidative stress. Histopathological examination showed improved neuronal function without toxicity. The results showed significant improvements (p < 0.001) in memory and cognitive abilities in experimental animals, highlighting the potential of ALN-βCD nanoparticles as a non-invasive treatment for memory loss. These promising findings warrant further exploration through clinical trials. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) constitute an important cause of morbidity and mortality globally, and India is no exception to this trend. With the ongoing aging of the population in India, there is a notable surge in the prevalence and impact of CVDs among older adults. This review is aimed at providing a comprehensive overview of the current knowledge concerning the prevalence, risk factors, and management of CVDs in the context of Indian older adults. The incidence of CVDs in India is not only alarming but also exhibits an upward trajectory with advancing age. Primary risk factors contributing to the elevated incidence among older adults include hypertension (HT), diabetes, dyslipidemia, obesity, smoking, a sedentary lifestyle, and poor dietary habits. Additionally, stress and genetic predisposition emerge as noteworthy contributors to CVDs in this population. Effectively identifying and managing these risk factors among older adults in India is imperative to alleviate the burden of these diseases and enhance overall quality of life. Strategies aimed at mitigating the impact of CVDs in the country necessitate a comprehensive approach, integrating lifestyle interventions, public health initiatives, and a robust healthcare system. In summary, CVDs represent a significant health concern in both rural and urban areas of India. However, variations exist in the prevalence, risk factors, and accessibility to healthcare between these regions. Therefore, addressing the prevalence of CVDs in India necessitates a complex, multidimensional strategy that takes into account the unique opportunities and challenges that come with living in both rural and urban areas. [ABSTRACT FROM AUTHOR]

The present study was aimed to develop chitosan-coated enamel adhesive device of CAP-P 407 (Cellulose acetate phthalate-Poloxamer 407), loaded with MNC (Minocycline) for sustained release and site-specific drug delivery system for the carious lesion. The average tensile strength and in-vitro drug release of uncoated dental film were found to be 15.97 kg/mm2 and 98.11% in 24 h, respectively. The average in-vitro mucoadhesion time and tooth adhesion strength of the finished product was found to be 249 minutes and 268 g, respectively. In-vitro antimicrobial study showed the drug concentration is well above MIC even after 8 hours of drug release. [ABSTRACT FROM AUTHOR]