Mannosylated gelatin nanoparticles bearing isoniazid for effective management of tuberculosis

Abstract

The mannosylated gelatin nanoparticles (Mn-GNPs) were prepared for the selective delivery of an antitubercular drug, isoniazid (INH), to the alveolar macrophages. The gelatin nanoparticles (GNPs) were prepared by using a two-step desolvation method and efficiently conjugated with mannose. Various parameters such as particle size, polydispersity index, zeta potential, % entrapment efficiency, in vitro drug release, macrophage uptake, in vivo biodistribution, antitubercular activity and hepatotoxicity of plain and Mn-GNPs were determined. The size of nanoparticles (both plain and Mn-GNPs) was found to be in range of 260–380 nm, and maximum drug payload was found to be 40–55%. Average particle size of Mn-GNPs was more, whereas drug entrapment was lesser compared to plain GNPs. The organ distribution studies demonstrated the efficiency of Mn-GNPs for spatial delivery of INH to alveolar tissues. Intravenous administration of INH loaded Mn-GNPs (I-Mn-GNPs) resulted in significant reduction in bacterial counts in the lungs and spleen of tuberculosis-infected (TB-infected) mice and also reduction in the hepatotoxicity of the drug. This study revealed that mannose conjugated GNPs may be explored as potential carrier for safer and efficient management of TB through targeted delivery of INH when compared to plain GNPs and free drug.

Keywords::

• Tuberculosis
• mannose
• isoniazid
• targeting
• alveolar macrophages

Acknowledgements

One of the authors (Gaurav Kant Saraogi) would like to thank National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Agra, India for providing extending facilities to perform FACS study and antitubercular activity and Indian Council of Medical Research (ICMR), New Delhi (India), for providing the financial assistance. Authors are grateful to M/s Lupin Ltd., Pune, India, for providing INH as a gift sample. Director, Electron Microscopy Section, AIIMS, New Delhi, India is acknowledged for providing the facilities for transmission electron microscopy.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.