Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria

Mol Pharm. 2024 May 6;21(5):2238-2249. doi: 10.1021/acs.molpharmaceut.3c01001. Epub 2024 Apr 15.

Abstract

Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.

Keywords: antibacterial; lipid extract; lipid reconstituted nanoparticles; mycobacterium membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology
  • Berberine / chemistry
  • Berberine / pharmacology
  • Cell Membrane / drug effects
  • Drug Carriers / chemistry
  • Drug Synergism
  • Lipids / chemistry
  • Microbial Sensitivity Tests
  • Mycobacterium / drug effects
  • Mycobacterium smegmatis* / drug effects
  • Mycobacterium tuberculosis / drug effects
  • Nanoparticles* / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer* / chemistry
  • Tuberculosis / drug therapy

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Lipids
  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Berberine
  • Drug Carriers