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

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Solid lipid nanoparticles containing anti-tubercular drugs attenuate the Mycobacterium marinum infection
Tuberculosis ( IF 2.8 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.tube.2020.102008
Sunil Khatak ₁ , Meenu Mehta ₂ , Rajendra Awasthi ₃ , Keshav Raj Paudel ₄ , Sachin Kumar Singh ₅ , Monica Gulati ₅ , Nicole G Hansbro ₆ , Philip M Hansbro ₆ , Kamal Dua ₇ , Harish Dureja ₈

Affiliation

Raj Kumar Goel Institute of Technology (Pharmacy), Ghaziabad, Uttar Pradesh, India; Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India.
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Centre for Inflammation, Centenary Institute, Sydney, NSW, 2050, Australia.
Amity Institute of Pharmacy, Amity University, Uttar Pradesh, Noida, 201313, India.
Centre for Inflammation, Centenary Institute, Sydney, NSW, 2050, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney (UTS), Ultimo, NSW, 2007, Australia.
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India.
Centre for Inflammation, Centenary Institute, Sydney, NSW, 2050, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney (UTS), Ultimo, NSW, 2007, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) & School of Biomedical Sciences and Pharmacy, The University of Newcastle (UoN), Callaghan, NSW, 2308, Australia.
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Centre for Inflammation, Centenary Institute, Sydney, NSW, 2050, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) & School of Biomedical Sciences and Pharmacy, The University of Newcastle (UoN), Callaghan, NSW, 2308, Australia; School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173229, India.
Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India.

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.

中文翻译：

含有抗结核药物的固体脂质纳米颗粒可减轻海分枝杆菌感染

本研究旨在使用微乳液技术配制用于口服给药的抗结核药物（利福平、异烟肼和吡嗪酰胺）负载的固体脂质纳米粒（ATDs-SLNs）。应用中心复合设计 (CCD) 来研究硬脂酸 (X1)、Compritol® 888 ATO (X2) 和泊洛沙姆 188: 牛磺胆酸钠 (% w/w) (X3) 等比例对粒径、zeta 电位的影响和截留效率。发现优化的配方 (SLN8) 呈球形，平均粒径为 187.9 ± 10.73 nm，zeta 电位为 -47.4 mV。发现优化配方中 RIF、INH 和 PYZ 的最大截留百分比分别为 86.40 ± 0.274、83.84 ± 0.269 和 81.43 ± 0.576。体外药物释放研究表明，与市售制剂和纯 ATD 相比，SLN 的药物释放缓慢。使用改良的 MTT 测定在鼠巨噬细胞系 (RAW 264.7) 上研究了 ATD-SLN 的细胞毒性，证明与标准抗结核药物相比，M. marinum 的生长抑制作用提高了两倍。总体而言，开发的前哨淋巴结可被视为一种有前途的抗分枝杆菌纳米药物，为结核病诊所提供了新的方向。

更新日期：2020-12-01

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