Folate Functionalized Lipid Nanoparticles for Targeted Therapy of Methicillin-Resistant Staphylococcus aureus.

Kushal Vanamala,David Andes,Razieh Kebriaei,Ketki Bhise,Samaresh Sau,Hosam Abdelhady,Michael J Rybak,Duy Luong,Hiram Sanchez,Arun K Iyer

doi:10.3390/pharmaceutics13111791

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), commonly called a superbug, is a highly alarming antibiotic-resistant population of Staphylococcus aureus (S. aureus) bacteria. Vancomycin (VAN) was first approved by the FDA in 1988, and it is still regarded as the treatment of choice for MRSA. The efficacy of VAN treatment has become less effective due to the development of VAN resistance in MRSA and the potential for nephrotoxicity. This study aims to improve the efficacy of VAN treatment by identifying the folate receptor for MRSA infected tissues and developing folate decorated lipid nanoparticles containing VAN (LVAN). In comparison to conventional VAN, LVAN showed a higher bactericidal effect and a superior ability to inhibit biofilm in MRSA with an enhanced accumulation in MRSA infected thigh tissues and a reduced accumulation in kidney. The results suggested that LVAN is a promising candidate to overcome the current limitations of bacterial resistance and adverse side effects in kidneys found in VAN.

Highlights

Staphylococcus aureus is a common human pathogen that normally dwells on the skin.Methicillin-resistant Staphylococcus aureus (MRSA) is a strain responsible for infections with limited, often ineffective treatment options due to the emergence of antibiotic resistance [1].While MRSA most commonly causes skin infections in the community setting, in healthcare settings it may cause infections of the bloodstream, surgical site infections, or pneumonia.In serious cases, it may lead to sepsis and death
We found that folate receptor (FR) expression is significantly increased in MRSA-infected animal tissue compared to uninfected control tissues
Literature evidence suggests that FR has a leading role in the induction of pro-inflammation, in MRSA infected sites, suggesting that FR could be a biomarker for infected sites [22,23,27]

Summary

Introduction

Staphylococcus aureus is a common human pathogen that normally dwells on the skin.Methicillin-resistant Staphylococcus aureus (MRSA) is a strain responsible for infections with limited, often ineffective treatment options due to the emergence of antibiotic resistance [1].While MRSA most commonly causes skin infections in the community setting, in healthcare settings it may cause infections of the bloodstream, surgical site infections, or pneumonia.In serious cases, it may lead to sepsis and death. Staphylococcus aureus is a common human pathogen that normally dwells on the skin. Methicillin-resistant Staphylococcus aureus (MRSA) is a strain responsible for infections with limited, often ineffective treatment options due to the emergence of antibiotic resistance [1]. While MRSA most commonly causes skin infections in the community setting, in healthcare settings it may cause infections of the bloodstream, surgical site infections, or pneumonia. In the US alone, annually, around 120,000 patients are diagnosed with, and 20,000 succumb to MRSA [2,3]. MRSA infected patient numbers increased to approximately 400,000 [4]. Infections caused by MRSA in both community and hospital settings is a matter of concern [5]

Objectives

Methods

Results

Conclusion