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. 2022 Nov 8;22(1):824.
doi: 10.1186/s12879-022-07791-8.

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

Zongqiang Yang #  1 , Caili Lou #  2 , Xuewei Wang  1 , Chaoran Wang  2 , Zhiyun Shi  3 , Ningkui Niu  4
Affiliations

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

Zongqiang Yang et al. BMC Infect Dis. .

Abstract

Background: Tuberculosis (TB) represents a bacterial infection affecting many individuals each year and potentially leading to death. Overexpression of transforming growth factor (TGF)-β1 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-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 the 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.

Keywords: Anti-tubercular drugs; Drug delivery; Nanoliposome; Spinal tuberculosis; TGF-β1 siRNA.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Particle size measured by DLS
Fig. 2
Fig. 2
A Zeta potential values for different weight ratios of HRZ nanoliposomes to loaded siTGF-β1. B Gel retardation data for different weight ratios of HRZ nanoliposomes to loaded siTGF-β1
Fig. 3
Fig. 3
TEM images of HRZ/siTGF-β1 nanoliposomes
Fig. 4
Fig. 4
HPLC data for (A) pre-preparation mixture of liposomes; (B) filtrate after liposome preparation
Fig. 5
Fig. 5
Cell viability of THP-1-derived macrophages after treatment with HRZ/siTGF-β1 nanoliposomes as assessed by the MTT assay. Notes: Survival of THP-1 derived macrophages treated with 0–50 mg/ml HRZ/siTGF-β1 nanoliposomes for 24 h. Data are mean ± SD of three independent experiments
Fig. 6
Fig. 6
Mechanisms of HRZ/siTGF-β1 nanoliposome-mediated inhibition of macrophage growth. Cell cycle distribution in macrophages after treatment with different nanoliposomes. *P < 0.05; **P < 0.01
Fig. 7
Fig. 7
Mechanisms of HRZ/siTGF-β1 nanoliposome-mediated inhibition of macrophage growth. Apoptosis in macrophages after treatment with different nanoliposomes. *P < 0.05; **P < 0.01
Fig. 8
Fig. 8
Effects of TGF-β1 knockdown measured by (A) qRT-PCR and (B) Western blot. siTGF-β1, siRNA targeting TGF-β1 mRNA; HRZ, control group of HRZ nanoliposomes; siNC, non-coding siRNA control group; Control, PBS group. *P < 0.05; **P < 0.01
See this image and copyright information in PMC

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