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.
Compound 4-(((6-amino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)methoxy)methyl)- 2,6-dimethoxyphenol (6) was synthesized by multi steps. The corresponding acetonitrile thioalkyl (7) was cyclized by refluxing with acetic acid to afford 4-(((6-amino-7H-[1,2,4]triazolo[3,4- b][1,3,4]thiadiazin-3-yl)methoxy)methyl)-2,6-dimethoxyphenol (8). Two new series of 4-(((6-(3- (4-aryl)thioureido)-7H-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazin-3-yl)methoxy)methyl)-2,6- dimethoxyphenol (9a-c) and of 4-(((6-(substitutedbenzamido)7H-[1,2,4]triazolo[3,4- b][1,3,4]thiadiazin-3-yl)methoxy)methyl)-2,6-dimethoxyphenol (10a-c) were synthesized as new derivatives for fused 1,2,4-trizaole-thiadiazine(8). The antioxidants of newly compounds were evaluated by DPPH
... Show MoreCompound 4-(((6-amino-7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (6) was synthesized by multi steps. The corresponding acetonitrile thioalkyl (7) was cyclized by refluxing with acetic acid to afford 4-(((6-amino-7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (8). Two new series of 4-(((6-(3-(4-aryl) thioureido)-7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (9a-c) and of 4-(((6-(substitutedbenzamido) 7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (10a-c) were synthesized as new derivatives for fused 1, 2, 4-trizaole-thiadiazine (8). The antioxidant
... Show MoreIn this study new derivatives of O-[2-{''2-Substituted Aryl (''1,''3,''4 thiadiazolyl) ['3,'4-b]-'1,'2,'4- Triazolyl]-Ethyl]-p- chlorobenzald oxime (6-11)have been synthesized from the starting material p-chloro – E- benzaldoxime 1.Compound 2 was synthesized by the reaction of p-chloro – E- benzaldoxime with ethyl acrylate in basic medium. Refluxing compound 2 with hydrazine hydrate in ethanol absolute afforded 3. Derivative 4 was prepared by the reaction of 3 with carbon disulphide, treated of compound 4 with hydrazine hydrate gave 5. The derivatives (6-11) were prepared by the reaction of 5 with different substitutesof aromatic acids. The structures of these compounds were characterized from their melting points, infrared spectroscopy
... Show MoreThe research aims to determine the required rate of return according to the Fama and French five-factor model, after strengthening it by adding the indebtedness factor to build the Fama and French six-factor model FF6M-DLE. The effect of the indebtedness factor on the company's profitability and the real value of the ordinary shares calculated according to the (equivalent ascertainment) model and its suitability with the company's situation, and an analysis of the fluctuation between the market value and the real value of the ordinary stocks.
Accelerates operating managements in the facilities contemporary business environment toward redefining processes and strategies that you need to perform tasks of guaranteeing them continue in an environment performance dominated by economic globalization and the circumstances of uncertainty attempt the creation of a new structure through multiple pages seek to improve profitability and sustainable growth in performance in a climatefocuses on the development of institutional processes, reduce costs and achieve customer satisfaction to meet their demands and expectations are constantly changing. The research was presented structural matrix performance combines methodology Alsigma in order to improve customer satisfaction significantly bet
... Show MoreDie Zusammenfassung :
In der Forschung „ Die Wirkungen der Nachkriegliteratur „ findet man einen Überblick über die Wirkungen der Literatur im Allgemeinen und besonders über die Wirkungen der Nachkriegliteratur in Deutschland. Das Kurzgeschichte „ das Brot“ von Wolfgang Borchert „ wird in dieser Forschung als Beispiel analysiuert, weil sie die Nachteile des Kriegs und ihre Wirkungen auf die Familienbeziehungen behandelt. Die Hauptfiguren der Kurzgeschichte sind ein alter Mann und seine Frau. Der Schriftsteller bestimmt die Rolle der Frauen in Deutschland. Die Frau in dieser Geschichte ist stärker als ihren Mann , denn er war lügner und schwach.
Post-war Literature has an e
... Show MoreThe research aims to identify small and medium enterprises in accounting thought in terms of definition and concept, and this international financial reporting standard for small and medium-sized enterprises (SMEs) in the theoretical aspect. As for the practical aspect, the small and medium-sized enterprises standard has been applied to the financial statements of the company in question, the preparation of the opening entry on the date of the transition, the requirements of measurement and the accounting disclosure on the date following the application of the standard, and the preparation of the company's financial statements and the accompanying explanations according to the standard of small and medium-sized enterprises. The r
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