In-vivo pharmacokinetic studies of Dolutegravir loaded spray dried Chitosan nanoparticles as milk admixture for paediatrics infected with HIV

Abstract

Dolutegravir (DTG) is an antiretroviral drug approved in the year 2013, and being categorized as a BCS-II molecule, it possesses solubility issues. In order to enhance the solubility and improve its bioavailability, DTG-loaded Chitosan nanoparticles (NPs) were synthesized utilizing spray drying technology. The developed nanoformulation was characterized for its physicochemical properties and investigated for the feasibility of its administration through an oral route along with milk/food as an admixture for paediatric antiretroviral therapy. The in vivo oral bioavailability studies were conducted in Balb-C mice, where the animals were treated with the selected formulation of DTG-loaded Chitosan NPs and compared to pure DTG. The NPs exhibited 2.5-fold increase in the Cmax (77.54 ± 7.93 μg/mL) when compared to the pure DTG (30.15 ± 8.06 μg/mL). This phenomenon was further reflected by the improved bioavailability of DTG (AUC: 678.3 ± 10.07 μg/h/mL) in the NPs administered to mice when compared to the AUC of animals administered with pure DTG (405.29 ± 7 μg/h/mL). Altogether, the research findings showed that Chitosan-based NPs were ideal carriers for oral administration of DTG along with milk and exhibited great potential to enhance the bioavailability of the drug and treatment adherence for paediatric HIV patients.

Polymer-based dual drug delivery system for targeted treatment of fluoroquinolone-resistant Staphylococcus aureus mediated infections

“…Accordingly, the TG curve displayed a gradual decrement in weight loss due to step-wise degradation of the sample followed by complete decomposition at 600°C with a residual weight of 1.070%. Overall, the purity and stability of the drug was not affected by entrapping in the polymeric nanoparticles formulation 52 (Fig. 6B).…”

“…The diffractogram of the nanoparticles displayed clusters of broad peaks in the same range for the 2-theta degree measurements. However, the intensity of the peaks was reduced and scattered, which indicated the transition of the drug from crystalline to semi-crystalline or amorphous state in the nanoparticles due to the encapsulation of the drug within the polymer matrix 52 .…”

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“…(S-4800, Hitachi Technologies Corporation, Japan). 1.5 kV of acceleration voltage is used to run the scanning electron microscope 18,19 .…”

Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir

“…Dolutegravir (DTG) is a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, which is combined with other antiretroviral agents for treating HIV-1 infection [ 27 ]. It is classified as BCS class II and has a low aqueous solubility [ 28 , 29 ]. The pKa of DTG is 8.2 and 10.1, which is weakly acidic; therefore, DTG remains primarily in a unionized form and, thus, poorly soluble all over the gastrointestinal tract (GIT).…”