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

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...

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Autores principales: Bhise, Ketki, Sau, Samaresh, Kebriaei, Razieh, Rice, Seth A., Stamper, Kyle C., Alsaab, Hashem O., Rybak, Michael J., Iyer, Arun K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073369/
https://www.ncbi.nlm.nih.gov/pubmed/30036944
http://dx.doi.org/10.3390/ma11071245
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author Bhise, Ketki
Sau, Samaresh
Kebriaei, Razieh
Rice, Seth A.
Stamper, Kyle C.
Alsaab, Hashem O.
Rybak, Michael J.
Iyer, Arun K.
author_facet Bhise, Ketki
Sau, Samaresh
Kebriaei, Razieh
Rice, Seth A.
Stamper, Kyle C.
Alsaab, Hashem O.
Rybak, Michael J.
Iyer, Arun K.
author_sort Bhise, Ketki
collection PubMed
description 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.
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spelling pubmed-60733692018-08-13 Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA Bhise, Ketki Sau, Samaresh Kebriaei, Razieh Rice, Seth A. Stamper, Kyle C. Alsaab, Hashem O. Rybak, Michael J. Iyer, Arun K. Materials (Basel) Article 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. MDPI 2018-07-20 /pmc/articles/PMC6073369/ /pubmed/30036944 http://dx.doi.org/10.3390/ma11071245 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bhise, Ketki
Sau, Samaresh
Kebriaei, Razieh
Rice, Seth A.
Stamper, Kyle C.
Alsaab, Hashem O.
Rybak, Michael J.
Iyer, Arun K.
Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA
title Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA
title_full Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA
title_fullStr Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA
title_full_unstemmed Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA
title_short Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA
title_sort combination of vancomycin and cefazolin lipid nanoparticles for overcoming antibiotic resistance of mrsa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073369/
https://www.ncbi.nlm.nih.gov/pubmed/30036944
http://dx.doi.org/10.3390/ma11071245
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