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Pharmacokinetic and Biomarker Quantification Studies on Vancomycin-Loaded PEGylated Liposomes and Its Potential to

Medha D Joshi1, Paulina Iacoban1, Marc H Scheetz2

  • 1College of Pharmacy, Midwestern University, Glendale Campus, 19555 N. 59th Avenue, Glendale, AZ 85308, USA.

Pharmaceutics
|June 28, 2023
PubMed

Insights

New liposome encapsulation of vancomycin (PEG-VANCO-lipo) significantly reduced kidney injury in rats compared to standard vancomycin. This novel formulation shows potential for safer vancomycin use, minimizing nephrotoxicity in clinical settings.

Area of Science:

  • Pharmacology and Toxicology
  • Drug Delivery Systems
  • Nephrology

Background:

  • Vancomycin is a critical antibiotic for Methicillin-resistant Staphylococcus aureus (MRSA) infections.
  • Vancomycin-induced nephrotoxicity is a significant adverse event in adult patients.
  • Drug concentration, particularly area under the curve, correlates with vancomycin-induced kidney injury.

Purpose of the Study:

  • To evaluate the efficacy of vancomycin encapsulated in polyethylene glycol-coated liposomes (PEG-VANCO-lipo) in reducing vancomycin-induced nephrotoxicity.
  • To compare plasma vancomycin concentrations and urinary KIM-1 levels between PEG-VANCO-lipo and conventional vancomycin HCl in a rat model.

Main Methods:

  • Male Sprague Dawley rats received either vancomycin HCl or PEG-VANCO-lipo (150 mg/kg/day) via IV infusion for three days.
  • Plasma vancomycin concentrations were measured at multiple time points post-infusion using LC-MS/MS.
  • Urinary KIM-1 levels, a biomarker for kidney injury, were assessed using ELISA kits.

Main Results:

  • Rats treated with PEG-VANCO-lipo exhibited significantly lower urinary KIM-1 levels and reduced vancomycin concentrations in urine and kidney tissue on day three compared to the vancomycin group (p < 0.05).
  • Plasma vancomycin concentrations were significantly reduced on days one and three in the vancomycin group compared to the PEG-VANCO-lipo group (p < 0.05).
  • PEG-VANCO-lipo demonstrated prolonged plasma circulation with higher plasma concentrations relative to kidney concentrations, correlating with decreased nephrotoxicity.

Conclusions:

  • Vancomycin-loaded PEGylated liposomes (PEG-VANCO-lipo) effectively reduce kidney injury biomarkers compared to standard vancomycin HCl.
  • The PEG-VANCO-lipo formulation results in altered pharmacokinetic profiles, favoring longer plasma circulation and reduced kidney accumulation.
  • PEG-VANCO-lipo holds significant potential for mitigating vancomycin-induced nephrotoxicity in clinical applications.
Keywords:
KIM-1kidneyliposomesnephrotoxicitypharmacokineticsvancomycin

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