Preparation, characterization, and in-vitro cytotoxicity of nanoliposomes loaded with anti-tubercular drugs and TGF-[beta]1 siRNA for improving spinal tuberculosis therapy

Tuberculosis (TB) represents a bacterial infection affecting many individuals each year and potentially leading to death. Overexpression of transforming growth factor (TGF)-[beta]1 has a primary immunomodulatory function in human tuberculosis. This work aimed to develop nanoliposomes to facilitate the delivery of anti-tubercular products to THP-1-derived human macrophages as Mycobacterium host cells and to evaluate drug efficiencies as well as the effects of a TGF-[beta]1-specific short interfering RNA (siRNA) delivery system employing nanoliposomes. In the current study, siTGF-[beta]1 nanoliposomes loaded with the anti-TB drugs HRZ (isoniazid, rifampicin, and pyrazinamide) were prepared and characterized in vitro, determining the size, zeta potential, morphology, drug encapsulation efficiency (EE), cytotoxicity, and gene silencing efficiency of TGF-[beta]1 siRNA. HRZ/siTGF-[beta]1 nanoliposomes appeared as smooth spheres showing the size and positive zeta potential of 168.135 [+ or -] 0.5444 nm and + 4.03 [+ or -] 1.32 mV, respectively. Drug EEs were 90%, 88%, and 37% for INH, RIF, and PZA, respectively. Meanwhile, the nanoliposomes were weakly cytotoxic towards human macrophages as assessed by the MTT assay. Nanoliposomal siTGF-[beta]1 could significantly downregulate TGF-[beta]1 in THP-1-derived human macrophages in vitro. These findings suggested that HRZ-loaded nanoliposomes with siTGF-[beta]1 have the potential for improving spinal tuberculosis chemotherapy via nano-encapsulation of anti-TB drugs.