Mechanisms of the effectiveness of lipid nanoparticle formulations loaded with anti-tubercular drugs combinations toward overcoming drug bioavailability in tuberculosis

Dual-drug-loaded lipid nanoparticle formulations (LNFs) namely solid lipid nanoparticles (SLNs) and nanostructured lipid carrier (are also solid lipid nanoparticles- a new generation of traditional SLNs) were developed and delivered to differentiated THP-1 cells. Developed LNFs have smooth and spherical surface morphology and nano range in size. In vitro drugs release profiles from these LNFs were slow and sustained. Particles were well co-localised in a different compartment (lysosome and endosome) of polarised macrophage by using suitable pH-dependent and antibody-mediated trafficking probe. Majority of the LNFs were also capable of existing in phago-lysosomal complex and able to effectively co-localise with the different cellular compartment of THP-1. The journey of the lipid carrier started through the formation of coated vesicle on differentiated macrophage surface, will further followed to idetify the efficient delivery of nano carrierat lysosomal and endosomal compartment in a sub cellular level of specific cell population. Comparative oral in vivo pharmacokinetic study revealed that nanostructured lipid carrier enhanced the pharmacokinetic profile compared to solid lipid nanoparticles and overall inclined the relative bioavailability by many folds. Cumulative results suggest that nanostructured lipid carrier could be an effective, alternative and promising lipid-mediated oral drug delivery approach than solid lipid nanoparticles.