Platensimycin-Encapsulated Liposomes or Micelles as Biosafe Nanoantibiotics Exhibited Strong Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus Infection in Mice.

Abstract

Platensimycin (PTM) is a promising natural product drug lead against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), while the clinical development was hampered by problems related to its poor solubility and pharmacokinetic properties. In this study, we used liposomes and micelles as carriers of PTM to prepare PTM nanoformulations for the treatment of MRSA infection in mice. PTM-loaded nanoparticles could effectively reduce residual bacteria in the MRSA-infected macrophage cell model, comparing to free PTM. More importantly, in vivo studies showed that encapsulation of PTM by liposomes or micelles effectively improved the pharmacokinetic properties of PTM in Sprague-Dawley rats and the survival rate of MRSA-infected C57BL/6J mice. Our study has thus suggested that the clinically used nanocarriers, such as liposome and micelle, might also be useful to improve the efficacy of other natural product drug leads to accelerate their in vivo evaluation and preclinical development.

• Authors: Zhe Wang, Xingyun Liu, Ying Peng, Meng Su, Saibin Zhu, Jian Pan, Ben Shen, Yanwen Duan, Yong Huang
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 17 Issue 7 Pg. 2451-2462 (07 06 2020) ISSN: 1543-8392 [Electronic] United States
• PMID: 32519867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminobenzoates
• Anilides
• Anti-Bacterial Agents
• Liposomes
• Micelles
• Nanocapsules
• Adamantane
• platensimycin

Topics

• Adamantane (administration & dosage, adverse effects, pharmacokinetics)
• Aminobenzoates (administration & dosage, adverse effects, pharmacokinetics)
• Anilides (administration & dosage, adverse effects, pharmacokinetics)
• Animals
• Anti-Bacterial Agents (administration & dosage, adverse effects, pharmacokinetics)
• Biofilms (drug effects)
• Cell Survival (drug effects)
• Drug Delivery Systems (methods)
• Drug Liberation
• Liposomes
• Macrophages (drug effects, metabolism, microbiology)
• Methicillin-Resistant Staphylococcus aureus (drug effects)
• Mice
• Mice, Inbred C57BL
• Micelles
• Nanocapsules (chemistry)
• RAW 264.7 Cells
• Rats
• Rats, Sprague-Dawley
• Staphylococcal Infections (drug therapy, metabolism, microbiology, mortality)
• Survival Rate