Nanoencapsulation of Antitubercular Drug Isoniazid and Its Lipopeptide Conjugate

Abstract

Isoniazid (INH) is a first line drug for treatment of the widespread deadly disease caused by Mycobacterium tuberculosis. Peptide conjugate of INH was designed and synthesised for targeted and receptor mediated cellular uptake of INH. Chemical composition, hydrophobicity (n-octanol/water partition coefficient), and membrane affinity (using a Langmuir lipid monolayer as a model system) of the conjugate were characterised. Hydrophilicity of the drug was remarkably decreased by the conjugation which resulted in improved interaction with lipid layer and allowed its efficient encapsulation into polylactic/glycolic acid nanoparticles enhancing the bioavailability of the drug.

Keywords:

• Antituberculotic drug conjugate
• drug encapsulation
• membrane affinity
• nanoprecipitation
• PLGA nanoparticles

Acknowledgments

The authors thank Zsolt Bendő for kind assistance with electron microscopy in SEM Laboratory of Centre of Earth Sciences, Eötvös Loránd University. Financial support of research programmes OTKA K68120, OTKA K68358, BIOSPONA TeT-08-SG-STAR, GVOP 3.2.1-2004-04-0099/3.0, and NKTH-TB-INTER is acknowledged.

Notes

*Number of samples = 5.

**Number of particles > 300.

*Calculated to INH content.

From the Proceedings from Formula VI in Stockholm 2010.