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.
Non-Small Cell Lung Cancer (NSCLC) accounts for about 84% of all lung cancer types diagnosed so far. Every year, regardless of gender, the NSCLC targets many communities worldwide. 5-Fluorouracil (5-FU) is a uracil-analog anticancer compound. This drug tends to annihilate multiple tumour cells. But 5-FU's most significant obstacle is that it gets very easily metabolized in the blood, which eventually leads to lower anticancer activity. Therfore a perfect drug delivery system is needed to overcome all the associated challenges.
In this experiment, an attempt was made to prepare 5-FU loaded poly lactic-co-glycolic acid nanoparticles using solvent evaporation method and subsequently observed the effect of molecular weight of poly l
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The most famous thing a person does is talk. He loves and hates, and continues with it confirming relationships, and with it, too, comes out of disbelief into faith. Marry a word and separate with a word. He reaches the top of the heavens with a kind word, with which he will gain the pleasure of God, and the Lord of a word that the servant speaks to which God writes with our pleasure or throws him on his face in the fire. Emotions are inflamed, the United Nations is intensified with a word, and relations between states and war continue with a word.
What comes out of a person’s mouth is a translator that expresses the repository of his conscience and reveals the place of his bed, for it is evidence of
... Show MoreAbstract: 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 MoreDNA 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;
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The research aims to identify the extent of the practice of social responsibility in accordance with the social dimension and diagnosis of constraints applied.
Find the problem represented by the Social Responsibility and obstacles facing application in Baghdad Municipality through their workers trends analysis.
The adoption of the statistical method to analyze the data and information gathering, and selected municipalities of Adhamiya and Kadhimiya deliberate manner applied as a state and municipal councils of both cities as representatives of the local community to be the subject of research and comparison between them to see the reality of soci
... Show MoreLow oil extraction and early high water production are caused in part by reservoir heterogeneity. Huge quantities of water production are prevalent issues that happen in older reservoirs. Polyacrylamide polymer gel systems have been frequently employed as plugging agents in heterogeneous reservoirs to regulate water output and increase sweep efficiency. Polyacrylamide polymer gel systems are classified into three classes depending on their composition and application conditions, which are in-situ monomer gel, in-situ polymer gel, and preformed particle gel (PPG).
This paper gives a comprehensive review of PPG’s status, preparation, and mechanisms. Many sorts of PPGs are categorized, for example, millimeter-sized preformed p
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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
This research studies the effect of adding micro, nano and hybrid by ratio (1:1) of (Al2O3,TiO2) to epoxy resin on thermal conductivity before and after immersion in HCl acid for (14 day) with normality (0.3 N) at weight fraction (0.02, 0.04, 0.06, 0.08) and thickness (6mm). The results of thermal conductivity reveled that epoxy reinforced by (Al2O3) and mixture (TiO2+Al2O3) increases with increasing the weight fraction, but the thermal conductivity (k) a values for micro and Nano (TiO2) decrease with increasing the weight fraction of reinforced, while the immersion in acidic solution (HCl) that the (k) values after immersion more than the value in before immersion.
The adsorption of Pb(II) ions onto bentonite and activated carbon was investigated. The effects of pH, initial adsorbent dosage, contact time and temperature were studied in batch experiments. The maximum adsorption capacities for bentonite and activated carbon were 0.0364 and 0.015 mg/mg, respectively. Thermodynamic parameters such as Gibbs free energy change, Enthalpy change and Entropy change have been calculated. These thermodynamic parameters indicated that the adsorption process was thermodynamically spontaneous under natural conditions and the adsorption was endothermic in nature. Experimental data were also tested in terms of adsorption kinetics, the results showed that the adsorption processes followed well pseudo second- order
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