Formulation, characterization, in vitro Anti-Tubercular activity and cytotoxicity study of solid lipid nanoparticles of isoniazid

Abstract

The present study was aimed to develop and optimize isoniazid (INZ) loaded solid lipid nanoparticles (SLNs) for exploring in vitro anti-tubercular and cytotoxic activity. The INZ-SLNs were successfully prepared by high pressure homogenization followed by ultrasonication technique and optimized using 23 full factorial designs. INZ-SLNs were characterized for particle size (PS), zeta potential (ZP), entrapment efficiency percentage (EE%) and cumulative percentage drug release (CDR%). Physicochemical properties were investigated using transmission electron microscopy (TEM), differential scanning calorimeter (DSC), X-ray diffraction and Fourier transmission infrared spectroscopy (FTIR). The average PS, ZP and EE% of the optimized formulation were found to be 167.1 nm, −32.4 mV and 73.17% respectively. The optimized formulation showed a CDR of 79.14% up to 36 h. In vitro anti-tubercular (luciferase reporter phage (LRP) assay in H37Rv viable and resistant strain) and cytotoxicity efficacy (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay in J774A.1 cells) of INZ-SLNs were evaluated and compared with free INZ. Results of LRP assay in H37Rv strain showed that percentage reduction in relative light unit (RLU) for INZ-SLNs and free INZ were 99.75 and 99.898% respectively, whereas in case of INZ resistant strain they were found to be 90.27 and 90.52% respectively, confirming notable antitubercular activity. MTT assay revealed that the percentage of cell viability upon exposure with INZ-SLNs was significantly higher (> 90%) than free INZ (< 80%), confirming its safety. Thus, INZ-SLNs could be an effective dosage form with sustained drug release profile, significant anti-tubercular activity, and reduced normal cell toxicity for achieving better therapeutic activity.