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

Sunil Khatak; Meenu Mehta; Rajendra Awasthi; Keshav Raj Paudel; Sachin Kumar Singh; Monica Gulati; Nicole G Hansbro; Philip M Hansbro; Kamal Dua; Harish Dureja

doi:10.1016/j.tube.2020.102008

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

Tuberculosis (Edinb). 2020 Dec:125:102008. doi: 10.1016/j.tube.2020.102008. Epub 2020 Oct 10.

Authors

Affiliations

¹ Raj Kumar Goel Institute of Technology (Pharmacy), Ghaziabad, Uttar Pradesh, India; Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India.
² Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Centre for Inflammation, Centenary Institute, Sydney, NSW, 2050, Australia.
³ Amity Institute of Pharmacy, Amity University, Uttar Pradesh, Noida, 201313, India.
⁴ 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.
⁵ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India.
⁶ 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.
⁷ 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. Electronic address: Kamal.Dua@uts.edu.au.
⁸ Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India. Electronic address: harishdureja@mdu.ac.in.

PMID: 33059322
DOI: 10.1016/j.tube.2020.102008

Abstract

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.

Keywords: Antitubercular drugs; Isoniazid; Pyrazinamide; Rifampicin; Solid lipid nanoparticles; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antitubercular Agents / administration & dosage
Antitubercular Agents / pharmacokinetics*
Disease Models, Animal
Mice
Microscopy, Electron, Scanning
Mycobacterium Infections, Nontuberculous / drug therapy
Mycobacterium Infections, Nontuberculous / microbiology*
Mycobacterium Infections, Nontuberculous / pathology
Mycobacterium marinum / drug effects
Mycobacterium marinum / isolation & purification*
Nanoparticles / ultrastructure*
Particle Size

Substances

Antitubercular Agents

Supplementary concepts

Infection with Mycobacterium marinum