Formulation and characterization of dolutegravir sodium-loaded nanostructured lipid carrier in situ gel for targeted brain delivery via intranasal route

Effective delivery of antiretroviral drugs to the brain is a major hurdle in treating central nervous system (CNS) HIV infections. This study developed an intranasal in situ gel containing dolutegravir sodium-loaded nanostructured lipid carriers (DTGs-NLCs) for targeted nose-to-brain delivery. DTGs-NLCs were prepared using a modified melt emulsification-ultrasonication method, yielding nanocarriers with a size of 80.8 ± 10.4 nm, zeta potential of –13±1.4 mV, and entrapment efficiency of 80.7 ± 0.48 %. These NLCs were incorporated into a thermosensitive in situ gel matrix composed of poloxamer 407 and carbopol 934P. The in vitro drug release from the gel was significantly enhanced compared to the free drug ( p < 0.05). Rheological studies confirmed the formulation’s non-Newtonian behavior, good spreadability (5.9 ± 0.13 cm), and strong mucoadhesiveness (1116.86 ± 20 dyne/cm²). Safety evaluations demonstrated excellent hemocompatibility and biocompatibility. Pharmacokinetic studies revealed that intranasal administration achieved higher brain concentrations (C max : 35.4 ± 3.6 µg/g; AUC₀–₄₈: 193.22±14.66 µg·h/g) and faster absorption (T max : 1 h) than intravenous delivery. These results indicate that the DTGs-NLC in situ gel offers a safe, non-invasive, and efficient approach for enhanced brain targeting, showing great promise for treating CNS complications of HIV, including neuroAIDS.