Nanoparticle encapsulated lipopeptide conjugate of antitubercular drug isoniazid: In vitro intracellular activity and in vivo efficacy in a guinea pig model of tuberculosis

Kata Horváti, Bernadett Bacsa, E. Kiss, Gergo Gyulai, Kinga Fodor, Gyula Balka, M. Rusvai, Eleonóra Szabó, F. Hudecz, Sz. Bősze

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Considering that Mycobacterium tuberculosis (Mtb) can survive in host phagocytes for decades and currently applied drugs are largely ineffective in killing intracellular Mtb, novel targeted delivery approaches to improve tuberculosis chemotherapy are urgently needed. In order to enhance the efficacy of a clinically used antitubercular agent (isoniazid, INH) a novel lipopeptide carrier was designed based on the sequence of tuftsin, which has been reported as a macrophage-targeting molecule. The conjugate showed relevant in vitro activity on Mtb H37Rv culture with low cytotoxicity and hemolytic activity on human cells. The conjugate directly killed intracellular Mtb and shows much greater efficacy than free INH. To improve bioavailability, the conjugate was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles and tested in vivo in a guinea pig infection model. External clinical signs, detectable mycobacterial colonies in the organs, and the histopathological findings substantiate the potent chemotherapeutic effect of orally administered conjugateloaded nanoparticles. (Figure Presented).

Original languageEnglish
Pages (from-to)2260-2268
Number of pages9
JournalBioconjugate Chemistry
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 17 2014

Fingerprint

Antitubercular Agents
Lipopeptides
Isoniazid
Mycobacterium tuberculosis
Nanoparticles
Guinea Pigs
Tuberculosis
Tuftsin
Polyglactin 910
Chemotherapy
Macrophages
Cytotoxicity
Cell culture
Cells
Molecules
Phagocytes
Human Activities
Pharmaceutical Preparations
Biological Availability
Drug Therapy

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Nanoparticle encapsulated lipopeptide conjugate of antitubercular drug isoniazid : In vitro intracellular activity and in vivo efficacy in a guinea pig model of tuberculosis. / Horváti, Kata; Bacsa, Bernadett; Kiss, E.; Gyulai, Gergo; Fodor, Kinga; Balka, Gyula; Rusvai, M.; Szabó, Eleonóra; Hudecz, F.; Bősze, Sz.

In: Bioconjugate Chemistry, Vol. 25, No. 12, 17.12.2014, p. 2260-2268.

Research output: Contribution to journalArticle

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