Comparison of the Efficacy of Two Novel Antitubercular Agents in Free and Liposome-Encapsulated Formulations

Int J Mol Sci. 2021 Feb 28;22(5):2457. doi: 10.3390/ijms22052457.


Tuberculosis is one of the top ten causes of death worldwide, and due to the appearance of drug-resistant strains, the development of new antituberculotic agents is a pressing challenge. Employing an in silico docking method, two coumaran (2,3-dihydrobenzofuran) derivatives-TB501 and TB515-were determined, with promising in vitro antimycobacterial activity. To enhance their effectiveness and reduce their cytotoxicity, we used liposomal drug carrier systems. Two types of small unilamellar vesicles (SUV) were prepared: multicomponent pH-sensitive stealth liposome (SUVmixed) and monocomponent conventional liposome. The long-term stability of our vesicles was obtained by the examination of particle size distribution with dynamic light scattering. Encapsulation efficiency (EE) of the two drugs was determined from absorption spectra before and after size exclusion chromatography. Cellular uptake and cytotoxicity were determined on human MonoMac-6 cells by flow cytometry. The antitubercular effect was characterized by the enumeration of colony-forming units on Mycobacterium tuberculosis H37Rv infected MonoMac-6 cultures. We found that SUVmixed + TB515 has the best long-term stability. TB515 has much higher EE in both types of SUVs. Cellular uptake for native TB501 is extremely low, but if it is encapsulated in SUVmixed it appreciably increases; in the case of TB515, quasi total uptake is accessible. It is concluded that SUVmixed + TB501 seems to be the most efficacious antitubercular formulation given the presented experiments; to find the most promising antituberculotic formulation for therapy further in vivo investigations are needed.

Keywords: 2,3-dihydrobenzofuran; absorption spectrometry; colony-forming units; coumaran; dynamic light scattering; flow cytometry; monocomponent liposome; pH-sensitive stealth liposome.

Publication types

  • Comparative Study

MeSH terms

  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Cell Proliferation
  • Cells, Cultured
  • Drug Compounding / methods*
  • Drug Delivery Systems*
  • Drug Design
  • Humans
  • Liposomes / administration & dosage*
  • Liposomes / chemistry
  • Monocytes / drug effects*
  • Mycobacterium tuberculosis / drug effects*
  • Tuberculosis / drug therapy*
  • Tuberculosis / microbiology


  • Antitubercular Agents
  • Liposomes