Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes

Methicillin-resistant Staphylococcus aureus (MRSA) can invade and survive in mammalian host cells, causing persistent and recurrent infections. Although vancomycin and gentamicin are potent against active extracellular MRSA, they are not effective against intracellular MRSA due to the low cellular u...

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Main Author: Chow, Yao Xiang
Other Authors: Loo Say Chye Joachim
Format: Final Year Project (FYP)
Language:English
Published: 2019
Subjects:
Online Access:http://hdl.handle.net/10356/76743
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author Chow, Yao Xiang
author2 Loo Say Chye Joachim
author_facet Loo Say Chye Joachim
Chow, Yao Xiang
author_sort Chow, Yao Xiang
collection NTU
description Methicillin-resistant Staphylococcus aureus (MRSA) can invade and survive in mammalian host cells, causing persistent and recurrent infections. Although vancomycin and gentamicin are potent against active extracellular MRSA, they are not effective against intracellular MRSA due to the low cellular uptake of the antimicrobials. Therefore, alternative antimicrobial approaches are being researched upon to eliminate these intracellular bacteria. One strategy is the use of delivery systems to carry these drugs directly to the target cells. Here, we propose a non-toxic lipid-polymer hybrid nanoparticle (LPN) system composed of a solid polymer core (i.e. PLGA; poly lactic-co-glycolic acid) and a cationic lipid shell (i.e. DOTAP) for localized, sustained release of antimicrobial agents to intracellular bacteria. LPNs were synthesized through a simple and robust self-assembly approach. Encapsulated gentamicin and vancomycin were more effective in eliminating intracellular MRSA compared to the free formulations. Cellular uptake of LPN was seen in both keratinocytes and macrophages, where the uptake level was higher in macrophages than that in keratinocytes. The novel formulations of this LPN system could be a useful method to enhance the efficiency of antimicrobial agents to eliminate intracellular bacteria.
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spelling ntu-10356/767432023-03-04T15:38:13Z Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes Chow, Yao Xiang Loo Say Chye Joachim School of Materials Science and Engineering Singapore Centre for Environmental Life Sciences Engineering DRNTU::Engineering::Materials::Biomaterials Methicillin-resistant Staphylococcus aureus (MRSA) can invade and survive in mammalian host cells, causing persistent and recurrent infections. Although vancomycin and gentamicin are potent against active extracellular MRSA, they are not effective against intracellular MRSA due to the low cellular uptake of the antimicrobials. Therefore, alternative antimicrobial approaches are being researched upon to eliminate these intracellular bacteria. One strategy is the use of delivery systems to carry these drugs directly to the target cells. Here, we propose a non-toxic lipid-polymer hybrid nanoparticle (LPN) system composed of a solid polymer core (i.e. PLGA; poly lactic-co-glycolic acid) and a cationic lipid shell (i.e. DOTAP) for localized, sustained release of antimicrobial agents to intracellular bacteria. LPNs were synthesized through a simple and robust self-assembly approach. Encapsulated gentamicin and vancomycin were more effective in eliminating intracellular MRSA compared to the free formulations. Cellular uptake of LPN was seen in both keratinocytes and macrophages, where the uptake level was higher in macrophages than that in keratinocytes. The novel formulations of this LPN system could be a useful method to enhance the efficiency of antimicrobial agents to eliminate intracellular bacteria. Bachelor of Engineering (Materials Engineering) 2019-04-08T07:49:29Z 2019-04-08T07:49:29Z 2019 Final Year Project (FYP) http://hdl.handle.net/10356/76743 en Nanyang Technological University 49 p. application/pdf
spellingShingle DRNTU::Engineering::Materials::Biomaterials
Chow, Yao Xiang
Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes
title Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes
title_full Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes
title_fullStr Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes
title_full_unstemmed Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes
title_short Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes
title_sort intracellular delivery of antibiotics to methicillin resistant staphylococcus aureus mrsa infected macrophages and keratinocytes
topic DRNTU::Engineering::Materials::Biomaterials
url http://hdl.handle.net/10356/76743
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