Co-delivery of dolutegravir and carbon-nanoparticles using niosomal platform for enhanced anti-HIV and pharmacokinetic activity.

The present study investigates the comparative evaluation of DTG-P, DTG-N and C-Np-DTG-N against HIV-1 infection. C-Np were synthesized from Buchanania lanzan leaves using a microwave-assisted method. The DTG-N formulation was optimized using central composite design and exhibited particle size, %EE and zeta potential of 124 nm, 80 %, and -32.7 mV respectively. The C-Np-DTG-N exhibited particle size and zeta potential of 134 nm and -37.5 mV respectively. Additionally, cytotoxicity studies were carried out in TZM-bl cells and human PBMCs where C-Np-DTG-N demonstrated greater efficacy against two different subtypes of HIV-1 strains (EC50 = 0.0032 µg/mL for HIV-1VB028 and 0.0036 µg/mL for HIV-1UG070) than DTG-P (EC50 = 0.0125 µg/mL for HIV-1VB028 and 0.0155 for HIV-1UG070). The confirmatory analysis using PBMCs validated the enhanced efficacy of C-Np-DTG-N. C-Np-DTG-N demonstrated highest inhibitory effect on HIV-1 integrase (89 %) compared to DTG-P (68.16 %). Furthermore, the pharmacokinetic and fluorescence spectroscopy studies were performed on adult, white New Zealand rabbits. C-Np-DTG-N exhibited a lower Cmax and a longer half-life (114.8 ng/mL and 34.3 h respectively) than DTG-N (144.82 ng/mL and 28.5 h) and DTG-P solution (157.4 ng/mL and 23.2 h respectively). AUC0-t and AUC 0-α of C-Np-DTG-N were greater (1109.8 ng/h/mL and 1370.2 ng/h/mL respectively) than DTG-N (1023.4 ng/h/mL and 1293.6 ng/h/mL) and DTG-P solution (942.7 ng/h/mL and 1205.1 ng/h/mL). Moreover, the Tmax of C-Np-DTG-N was longer (2 h) compared to DTG-N &DTG-P solution (1 h). Additionally, the fluorescence intensity of C-Np-DTG-N was higher (4721282 RFU) than C-Np alone (1035558 RFU after 48 h). This research suggests that C-Np-DTG-N offers an improved HIV therapy, providing enhanced anti-HIV activity and bioavailability compared to DTG & C-Np.