In vivo Brain Pharmacokinetics of Dolutegravir Sodium-Loaded Nanostructured Lipid Carrier in situ Gel: Comparative Study with an Intravenous Drug Solution

Salam Shanta Taher; Khalid Kadhem Al-Kinani

doi:10.54133/ajms.v8i1.1692

Authors

Salam Shanta Taher Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq https://orcid.org/0000-0003-1889-3073
Khalid Kadhem Al-Kinani Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq. https://orcid.org/0000-0002-1233-8944

DOI:

https://doi.org/10.54133/ajms.v8i1.1692

Keywords:

Dolutegravir sodium, HIV, in situ gel, NLC

Abstract

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 (C_max 35344.8ng/ml) compared to the IV solution (C_max 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 T_max) 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.

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