Background: Dolutegravir sodium (DTG), used to treat HIV, faces challenges in delivering effective therapeutic concentrations to the brain due to the blood-brain barrier (BBB). Nanostructured lipid carriers (NLCs) combined with in situ gels present a promising strategy for enhancing brain drug delivery via the intranasal route. Objective: To compare brain pharmacokinetics of DTGs delivered via NLC-loaded in situ gel intranasal administration with the conventional intravenous (IV) drug solution. Methods: 80 Wistar rats, which were divided into three groups: two groups consisting of 39 animals each and a control group with 2 animals. Rats were administered with a dose of 1.0 mg/kg of DTGs IV, and DTGs NLC-loaded in situ gel were administered intranasally. DTGs were determined in rats’ plasma and brain tissue by high-performance liquid chromatography (HPLC). Results: Intranasal administration produced significantly higher brain drug concentrations (Cmax 35344.8ng/ml) compared to the IV solution (Cmax 4536.85ng/ml). The area under the curve (AUC) for the intranasal formulation was twice that of the IV solution, indicating enhanced bioavailability. Furthermore, the intranasal route exhibited a faster onset (lower Tmax) and prolonged retention in brain tissue. The developed nanoformulation exhibited a Drug Targeting Efficiency (DTE) of 232.5% and a Drug Targeting Potential (DTP) of 57%, suggesting improved brain targeting efficiency. Conclusions: The DTGs-loaded NLC in situ gel shows superior brain pharmacokinetics compared to IV administration, highlighting its potential as an effective strategy for enhancing brain targeting.
Millions of pilgrims and visitors from numerous parts of the world flock to Karbala (one of the most prominent ideological and religious places in central Iraq) each year to visit the holy shrines in Karbala due to their sanctity. Many improvements have been made to the Two Holy Shrines (THS), the Shrines of Imam Husayn and Imam Abbas, and the area between them (ATHS), due to the high temperatures in this region and to improve pedestrian thermal comfort. Studies on improving outdoor thermal comfort in Karbala are scarce. Hence, this research aims to look into historical and current architectural changes and how they affect thermal comfort. On the hottest summer day, the ENVI-met software program was used to simulate the building des
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The study aims to identify the levels of core competencies dimensions and types of organizational flexibility in the investigated organization, as well as to determine the nature of the relationship and the impact of core competencies dimensions with the process of organizational flexibility. Thus, a number of research questions were presented to express the research problem as follows:
- What is the level of the investigated individuals' awareness to core competencies and organizational flexibility across their dimensions and types in the investigated organization?
- To what extent are core competencies and organizational flexibility available in the Organiz
Abstract: This study was aimed to investigate the effect of two doses of pregabalin (PGB) on hormonal level and sexual activity in female albino rats. Ninety female rats with age (9-10 weeks) and weight (200±20 g) were divided into three major groups of thirty rats. First group was considered as control G1, the second G2 and third G3 groups were exposed to PGB into two doses 150, and 300 mg/kg body weight per day respectively. Each major group was divided into three subgroups (subgroup A, B, and C of each has ten rats), the treatments last for one month for subgroup A, two months for subgroup B, and three months for subgroup C. Five rats from each subgroup were placed separately into two breeding cages with two isolated males and wait
... Show MoreRepresent choices Behaviorism available to the Managerial leaders one of the prerequisites to run any beginnings of a psychological or dilemmas Managerial barriers to working in the field of work has been varied these options until it had taken several kinds of which contributed to the left different impacts on the alleviation of these problems, which prompted the researcher to raising the problem of study within the framework of questionable content how to contribute to that shown by Choices Behaviorism accredited to the Managerial leaders in the management of frustration
... Show MoreEarly detection of brain tumors is critical for enhancing treatment options and extending patient survival. Magnetic resonance imaging (MRI) scanning gives more detailed information, such as greater contrast and clarity than any other scanning method. Manually dividing brain tumors from many MRI images collected in clinical practice for cancer diagnosis is a tough and time-consuming task. Tumors and MRI scans of the brain can be discovered using algorithms and machine learning technologies, making the process easier for doctors because MRI images can appear healthy when the person may have a tumor or be malignant. Recently, deep learning techniques based on deep convolutional neural networks have been used to analyze med
... Show MoreSeveral studies have claimed that AgNPs’ safety is not completely verified. The current work studied the CNS and renal genetic abnormalities (as manifested by modifications in NF-κB transcription) in mice treated with diverse AgNP concentrations. The findings revealed that as the amount of AgNPs was elevated, NF-κB production increased considerably.
DNA methylation is one of the main epigenetic mechanisms in cancer development and progression. Aberrant DNA methylation of CpG islands within promoter regions contributes to the dysregulation of various tumor suppressors and oncogenes; this leads to the appearance of malignant features, including rapid proliferation, metastasis, stemness, and drug resistance. The discovery of two important protein families, DNA methyltransferases (DNMTs) and Ten-eleven translocation (TET) dioxygenases, respectively, which are responsible for deregulated transcription of genes that play pivotal roles in tumorigenesis, led to further understanding of DNA methylation-related pathways. But how these enzymes can target specific genes in different malignancies;
... Show MoreKetoprofen has recently been proven to offer therapeutic potential in preventing cancers such as colorectal and lung tumors, as well as in treating neurological illnesses. The goal of this review is to show the methods that have been used for determining ketoprofen in pharmaceutical formulations. Precision product quality control is crucial to confirm the composition of the drugs in pharmaceutical use. Several analytical techniques, including chromatographic and spectroscopic methods, have been used for determining ketoprofen in different sample forms such as a tablet, capsule, ampoule, gel, and human plasma. The limit of detection of ketoprofen was 0.1 ng/ ml using liquid chromatography with tandem mass spectrometry, while it was 0
... Show MoreIn this research four steps of the new derivatives of Naproxen drug have been made which are known as a high medicinal effectiveness; the first step involved converting Naproxen into the corresponding ester (A) by reaction Naproxen with methanol absolute in presence H2SO4. While the second step involved treatment methyl Naproxen ester (A) with hydrazine hydrate 80% in presence of ethanol .The third reaction requires synthesis of Schiff bases (C1-C10) by condensation. of Naproxen hydrazide (B) with many substituted aromatic aldehydes . Finally, the fourth step synthesized new tetrazole derivatives ( D1- D10) by the reaction of the prepared Schiff bases (in the third step) with Sodium azide in THF as a solvent .The prepared compounds wer
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