Solid lipid nanoparticles containing anti-tubercular drugs attenuate the Mycobacterium marinum infection

The present study aimed to formulate anti-tubercular drugs (Rifampicin, Isoniazid and Pyrazinamide) loaded solid lipid nanoparticles (ATDs-SLNs) using microemulsion technique for oral administration. Central composite designed (CCD) was applied to study the effect of stearic acid (X₁), Compritol® 888 ATO (X₂) and equal ratio of poloxamer 188: sodium taurocholate (% w/w) (X₃) on particle size, zeta potential and entrapment efficiency. The optimised formulation (SLN₈) was found to be spherical in shape with mean particle size 187.9 ± 10.73 nm and zeta potential -47.4 mV. The maximum percentage entrapment of RIF, INH and PYZ in the optimised formulation was found to be 86.40 ± 0.274, 83.84 ± 0.269 and 81.43 ± 0.576, respectively. The in-vitro drug release study demonstrated that the release of drug from SLNs was slow in comparison to marketed formulation and pure ATDs. Cytotoxicity of the ATDs-SLNs was studied on murine macrophage cell line (RAW 264.7) using modified MTT assay demonstrated two folds growth inhibition of M. marinum as compared to standard antitubercular drugs. Overall, the developed SLNs may be considered as a promising anti-mycobacterial nano-drug, providing a new direction to the tuberculosis clinics.