Formulation Development and Characterization of Targeted Nano Drug Delivery Systems for the Treatment of Tuberculosis

Abstract

The oral delivery of anti-tubercular drugs remains challenging, despite being the most compliant route of administration. The main aim of current investigation demonstrates development of lung targeted surface tailored drug loaded solid lipid nanoparticles comprising of first line anti-TB agents. These drug loaded SLNs were developed and optimized by applying Design of Experiments. Significant independent variables like concentration of drug, concentration of emulsifier, homogenization cycles and homogenization pressure were identified and evaluation was statistically performed on dependent variables like %drug loading (%DL), %entrapment efficiency (%EE) and particle size. These developed drug loaded SLNs were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), %EE, %DL, DSC, FTIR and TEM analysis. These were further surface modified by coupling of mannose to the amine group of stearylamine-functionalized SLNs. The in vitro dissolution studies were performed and kinetic profile for drug loaded SLNs revealed mechanistic explanation mainly through diffusion and dissolution mechanism. The in vitro cytotoxicity studies were performed using J774A.1 cell line depicting that the developed SLNs were non-toxic and safe as compared to pure drug solution individually. Fluorescence imaging and flow cytometric analysis revealed remarkable intracellular uptake of coumarin-6 (fluorophore) loaded mannosylated SLNs at 9 h for all formulations. The in vivo pharmacokinetic studies in rats revealed that the mannosylated SLNs showed significant increase in relative bioavailability as compared to pure drug solution following oral administration. The in vivo biodistribution profiles revealed higher lung accumulation by Mannosylated SLNs as compared to unconjugated SLNs. Thus, it can be concluded that the developed drug loaded mannosylated SLNs could be used as a potential formulation for the treatment of tuberculosis.