Dual antitubercular drug loaded liposomes for macrophage targeting: development, characterisation, ex vivo and in vivo assessment

Abstract

Aim

The present study was conducted to formulate and investigate liposomes for the dual drug delivery based on anti-tubercular drug(s) combination i.e. Isoniazid (INH) and Rifampicin (RIF).

Materials and methods

Mannosylated and non mannosylated liposomes were prepared by lipid thin film hydration method, using DSPC: Chol at a molar ratio 6:4 while in case of mannosylated liposomes DSPC: Chol: Man-C4-Chol at a molar ratio 6.0:3.5:0.5 were used and extensively characterised. The particle size and zeta potential were recorded to be 1.29 ± 0.24 µm and −9.1 ± 0.11 mV. The drug entrapment (%) was recorded to be 84.7 ± 1.25% for Rifampicin and 31.8 ± 0.12% for Isoniazid.

Results

The antitubercular activity studied in Balb/C mice was maximum in the case of mannosylated liposomes. The biodistribution studies also revealed higher drug(s) concentration (accumulation) maintained over a protracted period.

Conclusions

The liposomal preparations are passively as well as actively uptaken by the alveolar macrophages which are the cellular tropics of infection. The mannosylated liposomes appear to be a potential carrier for dual drug delivery and targeted antitubercular therapy.

Keywords:

• Mycobacterium tuberculosis
• infectious disease
• mannosylated liposomes
• macrophages
• phagocytosis
• combination drug therapy
• active targeting

Acknowledgements

The authors acknowledge Dr. Shivendra K. Chaurasiya, Department of Biological Sciences and Engineering, Maulana Azad National Institute of Technology, Bhopal, India and Dr. Ruchi Paroha, Department of Microbiology and Cell biology, Indian Institute of Science, Bangalore, India for microbiological evaluations. The authors gratefully thank Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh, India and Department of Chemistry, Dr. Harisingh Gour University, Sagar, MP, India, for technical resources and instrumentations.

Disclosure statement

The authors declare no conflicts of interests.

Additional information

Funding

The author Priya Shrivastava is grateful to Department of Science and technology (DST, New Delhi), India [Grant Number: DST/INSPIRE Fellowship/2017/IF170447, Dated 16/01/2018] for financial support.