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Materials 2018, 11(7), 1245; https://doi.org/10.3390/ma11071245

Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA

1
Use-Inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA
2
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA
3
Department of Pharmacy Services, Detroit Medical Center, Detroit, MI 48201, USA
4
Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, MI 48201, USA
5
Molecular Imaging Program, Karmanos Cancer Institute, Detroit, MI 48201, USA
*
Author to whom correspondence should be addressed.
Received: 19 June 2018 / Revised: 12 July 2018 / Accepted: 17 July 2018 / Published: 20 July 2018
(This article belongs to the Special Issue Nanomaterials in Health Care Diagnostics)
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Abstract

Vancomycin is the treatment of choice for infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Clinically, combinations of vancomycin (VAN) and beta-lactams have been shown to improve patient outcomes compared to VAN alone for the treatment of MRSA bloodstream infections. However, VAN is known to cause nephrotoxicity, which could be ameliorated using biocompatible lipid drug delivery systems or liposomes. Previous attempts have been made for encapsulation of VAN in liposomes; however, drug loading has been poor, mainly because of the high aqueous solubility of VAN. In this study, we report a robust method to achieve high loading of VAN and cefazolin (CFZ) in unilamellar liposomes. Liposomes of sizes between 170–198 nm were prepared by modified reverse phase evaporation method and achieved high loading of 40% and 26% (weight/weight) for VAN and CFZ, respectively. Liposomal VAN reduced minimum inhibitory concentration (MIC) values 2-fold in comparison to commercial VAN. The combination of liposomal VAN (LVAN) and liposomal CFZ (LCFZ) demonstrated a 7.9-fold reduction compared to LVAN alone. Rhodamine dye-loaded liposomes demonstrated superior cellular uptake in macrophage-like RAW 264.7 cells. Fluorescent images of LVAN-encapsulating near-infrared (NIR) dye, S0456 (LVAN-S0456) clearly indicated that LVAN-S0456 had reduced renal excretion with very low fluorescent intensity in the kidneys. It is anticipated that the long circulation and reduced kidney clearance of LVAN-S0456 compared to VAN-S0456 injected in mice can lead to enhanced efficacy against MRSA infections with reduced nephrotoxicity. Overall, our developed formulations of VAN when administered alone or in combination with CFZ, provide a rational approach for combating MRSA infections. View Full-Text
Keywords: vancomycin; cefazolin; liposomes; nanoparticles; MRSA; macrophage; nephrotoxicity vancomycin; cefazolin; liposomes; nanoparticles; MRSA; macrophage; nephrotoxicity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Bhise, K.; Sau, S.; Kebriaei, R.; Rice, S.A.; Stamper, K.C.; Alsaab, H.O.; Rybak, M.J.; Iyer, A.K. Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA. Materials 2018, 11, 1245.

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