Enhancing Oral Bioavailability of Simvastatin Using Uncoated and Polymer-Coated Solid Lipid Nanoparticles.

Simvastatin (SVA) is a well-prescribed drug for treating cardiovascular and hypercholesterolemia. Due to the extensive hepatic first-pass metabolism and poor solubility, its oral bioavailability is 5%. Solid lipid nanoparticles (SLNs) and hydrogel-coated SLNs were investigated to overcome the limited bioavailability of SVA. Four different lipids used alone or in combination with two stabilizers were employed to generate 13 SLNs. Two concentrations of chitosan (CS) and alginate (AL) were coating materials. SLNs were studied for particle size, zeta potential, in vitro release, rheology, and bioavailability. The viscosities of both the bare and coated SLNs exhibited shear-thinning behavior. The viscosity of F11 (Chitosan 1%) at 20 and 40 rpm were 424 and 168 cp, respectively. F11 had a particle size of 260.1 ± 3.72 nm with a higher release; the particle size of F11-CS at 1% was 524.3 ± 80.31 nm. In vivo studies illustrated that F11 had the highest plasma concentration when compared with the SVA suspension and coated chitosan (F11 (Chitosan 1%)). Greater bioavailability is measured as (AUC0→24), as compared to uncoated ones. The AUC for F11, F11-CS 1%, and the SVA suspension were 1880.4, 3562.18, and 272 ng·h/mL, respectively. Both bare and coated SLNs exhibited a significantly higher relative bioavailability when compared to that from the control SVA.

Elemental analysis of levitated solid samples by microwave-assisted laser induced breakdown spectroscopy.

A novel analysis technique of elements at ambient conditions has been developed. The technique is based on microwave-assisted laser-induced breakdown spectroscopy (MW-LIBS) applied to acoustically levitated samples. The technique has been demonstrated using three solid samples with different properties and compositions. These are ore containing multiple elements (OREAS 520), aluminium oxide (Al3O2) and gypsum (CaSO4·2H2O). The mass of samples was 21 mg, 23 mg, and 55 mg for gypsum, mineral ore, and Al3O2, respectively. Significant signal enhancements were recorded for a variety of elements, using microwave-assisted laser-induced breakdown spectroscopy and levitation (MW-LIBS-Levitation). The signal enhancement for Mn I (403.07 nm), Al I (396.13 nm) and Ca II (393.85 nm) was determined as 123, 46, and 63 times, respectively. Moreover, it was found that MW-LIBS-Levitation minimises the self-absorption of the Ca I (422.67 nm) and Na I (588.99 nm and 589.59 nm) spectral lines. In addition to the signal enhancements, the levitation process produces a spinning motion in the solids with an angular frequency of 7 Hz. This feature benefits laser-based analysis as a fresh sample is introduced at each laser pulse, eliminating the need for the usual mechanical devices. Based on the single-shot analysis, it was found that ∼80% of the laser pulses produced successful MW-LIBS-Levitation detection, confirming an impressive repeatability of the process. This contactless analytical technique can be applied in ambient pressure and temperature conditions with high sensitivity, which can benefit disciplines such as forensics science, isotope analysis, and medical analysis, where the sample availability is often diminutive.

Factors Associated with Lifestyle Behaviors among University Students-A Cross-Sectional Study.

Lifestyle behaviors are daily habits influenced by social and environmental factors. This study examined lifestyle behaviors and their associations with sociodemographics, comorbidities, and pain in Saudi university students during the academic year 2021 and 2022. All students received the study invitation via university emails to complete an online questionnaire. The questionnaire included four sections (sociodemographics, health-related information, desired health promotion activities, and a lifestyle behavior assessment) via Health-Promoting Lifestyle Profile II (HPLP-II). The associations between study variables were assessed using Pearson's correlation and multiple linear regression. The study questionnaire was completed by 1112 students. No correlation was found between sociodemographics and lifestyle-behavior-related factors except for students in the College of Science who appeared to have good lifestyle behaviors (an increase in HPLP II total scores of 3.69). Students with mental health issues have poorer lifestyle behaviors and spend more time sitting (p < 0.00). Students without disabilities have lower scores in health responsibility, physical activity, nutrition, and stress management, while auditory disability specifically lowers health responsibility (p < 0.00). Pain was not associated with any assessed lifestyle behaviors. This study identified several significant correlations and differences between variables such as age, sedentary behavior, sleep duration, disability status, college major, and lifestyle behaviors among PNU students. These findings provide insights into the factors that influence students' health-promoting behaviors and can help guide interventions for promoting healthier lifestyles on campus. Targeted health promotion strategies at an early age could help in decreasing overall noncommunicable disease incidents later in life. The study results should be interpreted taking into consideration that the collected data were cross-sectional and self-reported. In conclusion, the findings of this study clearly demonstrate the need for specific lifestyle and health-promoting programs that are directed toward university students.

Prevalence and Risk Factors of Deep Vein Thrombosis Among Adult Surgical Patients in Aseer Central Hospital, Saudi Arabia.

INTRODUCTION: Deep vein thrombosis (DVT) is a medical disorder that arises when a coagulation of blood forms in a deep vein, entirely or partially blocking veins, and commonly affects the lower limb. The occurrence is fairly common worldwide and it is said to increase with age, with males being at a higher risk than females. OBJECTIVE: This study aims to determine the prevalence and risk factors of DVT among adult surgical patients in Aseer Central Hospital in the Aseer Region of Saudi Arabia. METHODS: This is a cross-sectional study involving 602 adult surgical patients hospitalized in the Aseer Central Hospital. Self-administered questionnaires were used to collect data from the respondents, and the data collected were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States). Statistical tests of association were used among the categorical variables. Association between variables was considered significant when p-value was less than 0.05. Binary logistic regression was performed to eliminate the effect of confounders in determining the risk factors for developing DVT among the respondents. RESULTS: The questionnaire response rate was 100%, with the mean age of the respondents being 44.2 ± 19.7 years. The prevalence of DVT was 7% (n=42). Obesity with adjusted OR (aOR) 17.9 (95%CI =5.39-59.18), hypertension with aOR 0.3 (95%CI =0.08-1.03), ischemic heart disease with aOR4.5 (95%CI =1.18-16.83), and orthopedics aOR 0.1 (95%CI=0.013-.240) were found to be independent risk factors for developing DVT among the respondents (p-value <=0.05). Other variables like diabetes, contraception, and pregnancy were not statistically associated with the development of DVT (p-value> 0.05) in these respondents. CONCLUSION: The findings of this study indicated a significantly low prevalence in comparison to Saudi Arabian research. Key risk factors included obesity (18x higher risk), ischemic heart disease, and hypertension. Surgery location, orthopedic cast, and Doppler ultrasound also influenced risk, while age and sex weren't significant predictors.

Sodium alginate-based smart gastro-retentive drug delivery system of revaprazan loaded SLNs; Formulation and characterization.

Revaprazan (REV), a novel reversible Proton Pump Inhibitor (PPI) used to treat peptic ulcers, faces challenges in therapeutic efficacy due to its poor dissolution properties and a short half-life. Solid lipid nanoparticles (SLNs) have emerged as a drug delivery system capable of enhancing dissolution and bioavailability of lipid soluble drugs. Here, we report on the development and optimization of a smart gastro-retentive raft system of REV-loaded SLNs (GRS/REV-SLNs) to enhance drug bioavailability and gastric retention. The optimized REV-SLNs had a particle size of 120 nm, a Polydispersity Index (PDI) of 0.313, a zeta potential of -20.7 mV, and efficient drug incorporation of 88 %. Transmission Electron Microscopy (TEM) affirmed the spherical morphology of these REV-SLNs, while Fourier Transform Infrared Spectroscopy (FTIR) revealed no chemical interactions among components. In-vitro assessment of the final GRS/REV-SLNs demonstrated sustained gelation and buoyancy for over 12 h, which would significantly enhance REV retention and its release within the stomach. Further assessments in rats confirmed successful gel transformation within the stomach, resulting in the improved bioavailability of REV. Thus, the development of GRS/REV-SLNs significantly improved the delivery and bioavailability of REV within the stomach, and offers a potentially improved method of treating peptic ulcers.

The Use of Nanoneedles in Drug Delivery: an Overview of Recent Trends and Applications.

Nanoneedles (NN) are growing rapidly as a means of navigating biological membranes and delivering therapeutics intracellularly. Nanoneedle arrays (NNA) are among the most potential resources to achieve therapeutic effects by administration of drugs through the skin. Although this is based on well-established approaches, its implementations are rapidly developing as an important pharmaceutical and biological research phenomenon. This study intends to provide a broad overview of current NNA research, with an emphasis on existing approaches, applications, and types of compounds released by these systems. A nanoneedle-based delivery device with great spatial and temporal accuracy, minimal interference, and low toxicity could transfer biomolecules into living organisms. Due to its vast potential, NN has been widely used as a capable transportation system of many therapeutic active substances, from cancer therapy, vaccine delivery, cosmetics, and bio-sensing nanocarrier drugs to genes. The use of nanoneedles for drug delivery offers new opportunities for the rapid, targeted, and exact administration of biomolecules into cell membranes for high-resolution research of biological systems, and it can treat a wide range of biological challenges. As a result, the literature has analyzed existing patents to emphasize the status of NNA in biological applications.

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. ß-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (ß- and hydroxy propyl ß-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-ß- and hydroxy propyl ß-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6')-Ib. The blaIMP and aac (6')-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.

Potential Candidate Genes for Therapeutic Targeting in Chronic Myeloid Leukemia: A Pilot Study.

BACKGROUND: Chronic myeloid leukemia (CML) is a prevalent hematological malignancy known for the presence of the Philadelphia chromosome and activation of the BCR-Abl kinase activity. Although tyrosine kinase inhibitors are widely used as the standard treatment, resistance remains a concern among certain patients. This study aimed to investigate the gene expression profile of a group of CML patients in comparison to a control group in order to identify novel candidate genes associated with the disease. METHODS: Whole transcriptome sequencing was performed, and gene expression levels were validated using quantitative real-time PCR. Additionally, single nucleotide and insertion/deletion variants were analyzed in the selected candidate genes among 10 CML patients and 4 healthy control subjects. RESULTS: Analysis revealed a set of differentially expressed genes, whose up- or downregulation was further confirmed by qRT-PCR. Among the upregulated genes in the patient group were ribosomal protein like (RPL) members, specifically RPL9, RPL34, RPL36A, and RPL39, while downregulation was observed in CCDC170, LDB1, and SBF1 compared to the healthy subjects. Furthermore, gene variant studies identified novel genetic changes in these candidate genes, suggesting potential clinical significance in CML. CONCLUSIONS: This study highlights RPL9, RPL34, RPL36A, RPL39, CCDC170, LDB1, and SBF1 as potential targets in CML. Additionally, it underscores the importance of investigating these genes and their variants in larger cohort studies to assess their clinical significance in CML patients.

Impact of Vitamin D Deficiency on Mental Health in University Students: A Cross-Sectional Study.

Students pursuing a university education are vulnerable to psychological burdens such as depression, anxiety, and stress. The frequency of vitamin D deficiency, on the other hand, is extensively recognized worldwide, and vitamin D regulates various neurological pathways in the brain that control psychological function. Therefore, the goal of this cross-sectional study was to determine the relationship between vitamin D deficiency and psychological burden among university students in Riyadh, Saudi Arabia. During March-May 2021 in Riyadh, a cross-sectional comparative study survey was delivered to university students. The DASS-21 scale was used to determine the severity of the psychological burden. Both univariate and binomial regression analyses were conducted to analyze the level of significance and influence of several factors on the development of psychological burden. The data were analyzed with SPSS-IBM, and a p value of <0.05 was considered significant. Of the 480 students recruited for the study, 287 (59.79%) had a vitamin D deficiency. Significantly (p = 0.048), a high proportion of the vitamin D-deficient students attained a low or moderate GPA compared to the control cohort. The prevalence of depression, anxiety, and stress among the vitamin D-deficient students was 60.35%, 6.31%, and 75.08%, respectively, which was significantly (p < 0.05) different from the control group. The odds of developing depression (OR = 4.96; CI 2.22-6.78; p < 0.001), anxiety (OR = 3.87; CI 2.55-6.59; p < 0.001), and stress (OR = 4.77; CI 3.21-9.33; p < 0.001) were significantly higher in the vitamin D-deficient group. The research shows a strong association between psychological stress and vitamin D deficiency. To promote the mental health and psychological wellbeing of university students, it is critical to create awareness about the adequate consumption of vitamin D. Additionally, university students should be made aware of the likelihood of a loss in academic achievement owing to vitamin D deficiency, as well as the cascade effect of psychological burden.

Novel Rhinological Application of Polylactic Acid-An In Vitro Study.

A novel approach to the treatment of sinusitis is the use of nasal stents. The stent is loaded with a corticosteroid, which prevents complications in the wound-healing process. The design is such that it will prevent the sinus from closing again. The stent is 3D printed using a fused deposition modeling printer, which enhances the customization. The polymer utilized for the purpose of 3D printing is polylactic acid (PLA). The compatibility between the drugs and polymers is confirmed by FT-IR and DSC. The drug is loaded onto the polymer by soaking the stent in the drug's solvent, known as the solvent casting method. Using this method, approximately 68% of drug loading is found to be achieved onto the PLA filaments, and a total of 72.8% of drug loading is obtained in terms of the 3D-printed stent. Drug loading is confirmed by the morphological characteristics of the stent by SEM, where the loaded drug is clearly visible as white specks on the surface of the stent. Drug release characterization is conducted by dissolution studies, which also confirm drug loading. The dissolution studies show that the release of drugs from the stent is constant and not erratic. Biodegradation studies were conducted after increasing the rate of degradation of PLA by soaking it in PBS for a predetermined duration of time. The mechanical properties of the stent, such as stress factor and maximum displacement, are discussed. The stent has a hairpin-like mechanism for opening inside the nasal cavity.

Evaluation of solid-lipid nanoparticles formulation of methotrexate for anti-psoriatic activity.

Background & Objectives: Methotrexate (MTX) is commonly used to manage psoriasis. The drug has erratic absorption characteristics and shows several complications. The present study uses different experimental models to evaluate the solid-lipid nanoparticles of MTX (SLN-MTX) for the anti-psoriatic effect. Methods: A prepared SLN-MTX formulation was used and its permeability studies were conducted on Wistar rat abdominal skin. The organ-level distribution of the drug in the formulation was tested in mice and the in-vitro anti-psoriatic activity was determined in CL-177; XB-2 keratinocytes cell lines. The efficacy of SLN-MTX formulation was compared with standard MTX and marketed MTX preparations. The results are analyzed statistically using the student's t-test. Results: The data suggested that MTX from the formulation was slowly released and completely (80.36%) permeated through the skin. The flux and permeation data were found to be maximum for SLN-MTX compared to marketed and standard preparations. MTX in the formulation was found to be distributed more in the liver (67.5%) and kidney (2.34%). Further, SLN-MTX formulation showed dose-dependent inhibition on the growth of keratinocytes, and the cytotoxic concentration (CTC50) was found to be the least (518 mcg/ml). Interpretation & Conclusion: The findings suggested that MTX in solid-lipid nanoparticles could be a promising formulation for the management of psoriasis since the drug was slowly released, progressively inhibited the growth of keratinocytes, and distributed mostly in organs meant for elimination. More studies in this direction might establish the precise safety and efficacy of SLN-MTX formulation in psoriasis.

A detailed insight of the tumor targeting using nanocarrier drug delivery system.

Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.

Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.

M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention.

Design, Physical Characterizations, and Biocompatibility of Cationic Solid Lipid Nanoparticles in HCT-116 and 16-HBE Cells: A Preliminary Study.

In this study, pEGFP-LUC was used as a model plasmid and three distinct cationic lipids (dioleyloxy-propyl-trimethylammonium chloride [DOTMA], dioleoyl trimethylammonium propane [DOTAP], and cetylpyridinium chloride [CPC]) were tested along with PEG 5000, as a nonionic surfactant, to prepare glyceryl monostearate (GMS)-based cationic solid lipid nanoparticles (cSLNs). Both the type and quantity of surfactant had an impact on the physicochemical characteristics of the cSLNs. Thermal analysis of the greater part of the endothermic peaks of the cSLNs revealed they were noticeably different from the individual pure compounds based on their zeta potential (ZP ranging from +17 to +56 mV) and particle size (PS ranging from 185 to 244 nm). The addition of cationic surfactants was required to produce nanoparticles (NPs) with a positive surface charge. This suggested that the surfactants and extensive entanglement of the lipid matrix GMS provided support for the behavioral diversity of the cSLNs and their capacity to interface with the plasmid DNA. Additionally, hemolytic assays were used to show that the cSLNs were biocompatible with the human colon cancer HCT-116 and human bronchial epithelial 16-HBE cell lines. The DOTMA 6-based cSLN was selected as the lead cSLN for further ex vivo and in vivo investigations. Taken together, these new findings might provide some guidance in selecting surfactants to prepare extremely efficient and non-toxic cSLN-based therapeutic delivery systems (e.g., gene therapy).

Formulation development of lipid polymer hybrid nanoparticles of doxorubicin and its in-vitro, in-vivo and computational evaluation.

The purpose of this study was to assess the parameters of doxorubicin (DOX) loaded lipid polymer hybrid nanoparticles (LPHNs) formulation development, and then the bioavailability of DOX were determined in the rabbit model, in order to evaluate the intrinsic outcome of dosage form improvement after the oral administration. LPHNs were prepared by combine approach, using both magnetic stirring and probe sonication followed by its characterization in terms of size-distribution (Zeta Size), entrapment efficiency (EE), loading capacity, and the kinetics of DOX. LPHNPs were further characterized by using scanning electron microscopy (SEM), powder X-Ray diffractometry (P-XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), in vitro and in vivo studies. The molecular modeling was determined through the density functional theory (DFT) simulations and interactions. DOX loaded and unloaded LPHNs were administered orally to the rabbits for bioavailability and pharmacokinetic parameters determinations. The plasma concentration of DOX was determined through high performance liquid chromatography (HPLC). The average size of DOX-loaded LPHNs was 121.90 ± 3.0 nm. The drug loading of DOX was 0.391% ± 0.01 of aqueous dispersion, where its encapsulation efficiency was 95.5% ± 1.39. After oral administration of the DOX-LPHNs, the area under the plasma drug concentration-time curve (AUC) improved about 2-folds comparatively (p < 0.05). DFT simulations were used to understand the interactions of polymers with different sites of DOX molecule. The larger negative binding energies (-9.33 to -18.53 kcal/mol) of the different complexes evince that the polymers have stronger affinity to bind with the DOX molecule while the negative values shows that the process is spontaneous, and the synthesis of DOX-LPHNs is energetically favorable. It was concluded that DOX-LPHNs provides a promising new formulation that can enhance the oral bioavailability, which have optimized compatibilities and improve the pharmacokinetic of DOX after oral administration.

Enhancing plant-derived smart nano inhibitor in targeting mammalian target of rapamycin (mTOR) in breast cancer using Curcuma longa-derived compound curcumin.

Breast cancer is a diverse female malignancy; its classification is based on clinical evidence and pathological elucidation. Large public drug screening data databases combined with transcriptome measures have helped develop predictive computational models. Breast cancer is frequent among women worldwide. Several genes increase breast cancer risk. The Mammalian Target of Rapamycin (popularly known as mTOR) is a risk factor mutated in numerous breast carcinoma types. This has caught the scientific community's focus, which is attempting to generate creative, potent, and bio-available ligands for future anti-cancer treatments to establish a practical therapeutic approach. mTOR is a protein kinase involved in cell proliferation, survival, metabolism, and immune response. Activating mTOR promotes cancer growth and spread. To generate a bioavailable and effective mTOR inhibitor, we used computer-aided drug design to study chromones and flavonoids, two naturally occurring chemicals with many biological activities. We used Curcuma longaderived tiny nano-molecules, which can be coated using liposomes to target mTOR to prevent breast cancer growth. The significant interactions of Curcumin were anticipated using molecular docking. It had the highest binding affinity at -12.26 kcal/mol. 100 nanoseconds of molecular dynamic modelling confirmed Curcumin and mTOR receptor interaction. Liposomes are a form of medicine carrier. To improve healthcare, more liposome-like nanostructures are being made. Nanostructures' interactions with living creatures are being studied. Half-life, tissue accumulation, and toxicity have been studied. Future medication distribution may use nanocarriers having a liposome-like form, enabling targeted nano-delivery. Curcumin's interaction with the active site increased the complex's structural stability during its expansion. Our results may help future investigations of Curcumin's efficacy as a possible lead treatment targeting mTOR receptors in breast cancer. Using Curcumin as a potential anti-cancer drug with lipid-coated nano-particles allows for tailored administration.

Development and Evaluation of Solid Lipid Nanoparticles for the Clearance of Aß in Alzheimer's Disease.

Aggregation of Amyloid-ß (Aß) 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 Aß on SHSY5Y cells in rat hippocampus. Molecular docking and in vitro Aß fibrillation were used to ensure the binding of drugs to Aß. 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 Aß (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 Aß plaques in rat hippocampus. Furthermore, the levels of Aß 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.

Nanotechnological synergy of mangiferin and curcumin in modulating PI3K/Akt/mTOR pathway: a novel front in ovarian cancer precision therapeutics.

Background: Ovarian cancer, colloquially termed the "silent killer" among gynecological malignancies, remains elusive due to its often-asymptomatic progression and diagnostic challenges. Central to its pathogenesis is the overactive PI3K/Akt/mTOR signaling pathway, responsible for various cellular functions, from proliferation to survival. Within this context, the phytochemical compounds mangiferin (derived from Mangifera indica) and curcumin (from Curcuma longa) stand out for their potential modulatory effects. However, their inherent bioavailability challenges necessitate innovative delivery systems to maximize therapeutic benefits. Objective: This study seeks to synergize the merits of nanotechnology with the therapeutic properties of mangiferin and curcumin, aiming to bolster their efficacy against ovarian cancer. Methods: Employing specific nanotechnological principles, we engineered exosomal and liposomal nano-carriers for mangiferin and curcumin, targeting the PI3K/Akt/mTOR pathway. Molecular docking techniques mapped the interactions of these phytochemicals with key proteins in the pathway, analyzing their binding efficiencies. Furthermore, molecular dynamics simulations, spanning 100 nanoseconds, verified these interactions, with additional computational methodologies further validating our findings. The rationale for the 100 nanoseconds time span lies in its sufficiency to observe meaningful protein-ligand interactions and conformational changes. Notably, liposomal technology provided an enhancement in drug delivery by protecting these compounds from degradation, allowing controlled release, and improving cellular uptake. Results: Our computational investigations demonstrated notable binding affinities of mangiferin and curcumin: PI3K at -11.20 kcal/mol, Akt at -15.16 kcal/mol, and mTOR at -10.24 kcal/mol. The adoption of exosome/liposome-mediated delivery significantly amplified the bioavailability and cellular uptake of these nano-formulated compounds, positioning them as potential stalwarts in ovarian cancer intervention. A brief explanation of exosome/liposome-mediated delivery involves the use of these vesicles to encapsulate and transport therapeutic agents directly to the target cells, enhancing drug delivery efficiency and minimizing side effects. Conclusion: Addressing ovarian cancer's intricacies, dominated by the erratic PI3K/Akt/mTOR signaling, mandates innovative therapeutic strategies. Our pioneering approach converges nanotechnological liposomal delivery with mangiferin and curcumin's natural efficacies. This confluence, validated by computational insights, heralds a paradigm shift in ovarian cancer treatment. As our findings underscore the collaborative potential of these phytochemicals, it beckons further exploration in translational studies and clinical applications, ensuring the best intersection of nature and technology for therapeutic advantage.

Perception of Healthcare Providers during the COVID-19 Pandemic: A Mixed Method Survey in an Integrated Healthcare Delivery System in Saudi Arabia.

During the COVID-19 pandemic, telemedicine was broadly adopted for patient care. Considering this experience, it is crucial to understand the perceptions of teleclinic healthcare professionals. In Saudi Arabia, telemedicine literature was restricted to physicians working in government and private hospitals. This study examined perceptions in relation to telemedicine among physicians and other healthcare professionals practicing in Saudi Arabian military hospitals in the Taif region. During COVID-19, telemedicine was implemented in military hospitals; consequently, this study assists in evaluating introduced practices and the perceptions of health professionals regarding these new practices. A quantitative, descriptive, correlational, and cross-sectional study was undertaken on healthcare professionals (N = 153). Twenty (20) items based on standardized measures were used to collect data using an online questionnaire. The measures contained three subscales: perceived usefulness, perceived ease, and behavioral intention. It was hypothesized that the perception of teleclinic usefulness and ease score by healthcare providers would be significantly correlated with behavioral intention. Descriptive statistics for mean, frequency, and standard deviation, as well as a Pearson correlation coefficient and regression analysis, were conducted to assess the relationship and predictive association between variables. In addition, a focus group discussion was organized to collect information directly from healthcare professionals. Most of the participants were approximately 40 years of age, Saudi Nationals (63%), medical specialists (62%), and were involved in teleclinic practices before the COVID-19 pandemic (60%). The reliability of all three scales was determined to be acceptable (α = 0.75-0.91). Perceived usefulness and perceived ease were shown to be significantly correlated with behavioral intention (r = 0.877, p = 0.05). In addition, the regression analysis indicated that perceived usefulness and perceived ease are predictors of the behavioral intention (R2 = 0.777, F (2,152) = 261.76, p = 0.001) of teleclinic practices among healthcare professionals. The positive perception of telemedicine integration in healthcare systems revealed by this study is a major catalyst for continuous adoption. On the other hand, certified telemedicine platforms, on-the-job training, Internet of things, and a flexible approach are required to find opportunities and enhancements in telemedicine interactions.

Carvedilol Precipitation Inhibition by the Incorporation of Polymeric Precipitation Inhibitors Using a Stable Amorphous Solid Dispersion Approach: Formulation, Characterization, and In Vitro In Vivo Evaluation.

An amorphous solid dispersion (ASD) of carvedilol (CVL) was prepared via the solvent evaporation method, using cellulose derivatives as polymeric precipitation inhibitors (PPIs). The prepared ASDs existed in the amorphous phase, as revealed by X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). The Fourier-transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) results confirmed the compatibility between CVL and the polymers used. The ASDs characteristics were evaluated, with no change in viscosity, a pH of 6.8, a polydispersity index of 0.169, a particle size of 423-450 nm, and a zeta potential of 3.80 mV. Crystal growth inhibition was assessed for 180 min via an infusion precipitation study in simulated intestinal fluid (SIF). The interactions between the drug and polymers were established in great detail, using nuclear magnetic resonance (NMR) spectroscopy, nuclear Overhauser effect spectroscopy (NOESY), and Raman spectroscopy studies. Dielectric analysis was employed to determine the drug-polymer interactions between ion pairs and to understand ion transport behavior. In vivo oral kinetics and irritation studies performed on Wistar rats have demonstrated promising biocompatibility, stability, and the enhanced bioavailability of CVL. Collectively, the stable ASDs of CVL were developed using cellulose polymers as PPIs that would inhibit drug precipitation in the gastrointestinal tract and would aid in achieving higher in vivo drug stability and bioavailability.