Preparation, characterrization, and in-vitro cytotoxicity of nanoliposomes loaded with anti-tuberculous drugs and TGF-β1 siRNA for improving spinal tuberculosis therapy

Abstract Background: Tuberculosis (TB) represents a bacterial infection affecting many individuals each year and potentially leading to death. Over expression of transforming growth factor (TGF)-β1 has a major immunomodulatory function in human tuberculosis. This work aimed to develop nanoliposomes to facilitate the delivery of antituberculous products to THP-1-derived human macrophages as Mycobacterium host cells, and to evaluate drug efficiencies as well as the effects of a TGF-β1-specific short interfering RNA (siRNA) delivery system employing nanoliposomes. Methods: In the current study, siTGF-β1 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-β1 siRNA. Results: HRZ/siTGF-β1 nanoliposomes appeared as smooth spheres showing size and positive zeta potential of 168.135±0.5444 nm and +4.03±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-β1 could significantly downregulate TGF-β1 in THP-1-derived human macrophages in vitro . Conclusion: These findings suggested that HRZ-loaded nanoliposomes with siTGF-β1 have the potential for improving spinal tuberculosis chemotherapy via nano-encapsulation of anti-TB drugs.