Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages
Intracellular bacteria are inaccessible and highly tolerant to antibiotics, hence are a major contributor to the global challenge of antibiotic resistance and recalcitrant clinical infections. This, in tandem with stagnant antibacterial discovery, highlights an unmet need for new delivery technologi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1037 |
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| author | Manasi Jambhrunkar Sajedeh Maghrebi Divya Doddakyathanahalli Anthony Wignall Clive A. Prestidge Kristen E. Bremmell |
| author_facet | Manasi Jambhrunkar Sajedeh Maghrebi Divya Doddakyathanahalli Anthony Wignall Clive A. Prestidge Kristen E. Bremmell |
| author_sort | Manasi Jambhrunkar |
| collection | DOAJ |
| description | Intracellular bacteria are inaccessible and highly tolerant to antibiotics, hence are a major contributor to the global challenge of antibiotic resistance and recalcitrant clinical infections. This, in tandem with stagnant antibacterial discovery, highlights an unmet need for new delivery technologies to treat intracellular infections more effectively. Here, we compare the uptake, delivery, and efficacy of rifampicin (Rif)-loaded mesoporous silica nanoparticles (MSN) and organo-modified (ethylene-bridged) MSN (MON) as an antibiotic treatment against small colony variants (SCV) <i>Staphylococcus aureus</i> (<i>SA</i>) in murine macrophages (RAW 264.7). Macrophage uptake of MON was five-fold that of equivalent sized MSN and without significant cytotoxicity on human embryonic kidney cells (HEK 293T) or RAW 264.7 cells. MON also facilitated increased Rif loading with sustained release, and seven-fold increased Rif delivery to infected macrophages. The combined effects of increased uptake and intracellular delivery of Rif by MON reduced the colony forming units of intracellular SCV-SA 28 times and 65 times compared to MSN-Rif and non-encapsulated Rif, respectively (at a dose of 5 µg/mL). Conclusively, the organic framework of MON offers significant advantages and opportunities over MSN for the treatment of intracellular infections. |
| first_indexed | 2024-03-11T04:38:12Z |
| format | Article |
| id | doaj.art-588f3ce044aa41b3810cbcbdf243891e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:38:12Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-588f3ce044aa41b3810cbcbdf243891e2023-11-17T20:51:48ZengMDPI AGPharmaceutics1999-49232023-03-01154103710.3390/pharmaceutics15041037Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in MacrophagesManasi Jambhrunkar0Sajedeh Maghrebi1Divya Doddakyathanahalli2Anthony Wignall3Clive A. Prestidge4Kristen E. Bremmell5Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaCentre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaCentre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaCentre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaCentre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaCentre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaIntracellular bacteria are inaccessible and highly tolerant to antibiotics, hence are a major contributor to the global challenge of antibiotic resistance and recalcitrant clinical infections. This, in tandem with stagnant antibacterial discovery, highlights an unmet need for new delivery technologies to treat intracellular infections more effectively. Here, we compare the uptake, delivery, and efficacy of rifampicin (Rif)-loaded mesoporous silica nanoparticles (MSN) and organo-modified (ethylene-bridged) MSN (MON) as an antibiotic treatment against small colony variants (SCV) <i>Staphylococcus aureus</i> (<i>SA</i>) in murine macrophages (RAW 264.7). Macrophage uptake of MON was five-fold that of equivalent sized MSN and without significant cytotoxicity on human embryonic kidney cells (HEK 293T) or RAW 264.7 cells. MON also facilitated increased Rif loading with sustained release, and seven-fold increased Rif delivery to infected macrophages. The combined effects of increased uptake and intracellular delivery of Rif by MON reduced the colony forming units of intracellular SCV-SA 28 times and 65 times compared to MSN-Rif and non-encapsulated Rif, respectively (at a dose of 5 µg/mL). Conclusively, the organic framework of MON offers significant advantages and opportunities over MSN for the treatment of intracellular infections.https://www.mdpi.com/1999-4923/15/4/1037antibacterialmesoporous silica nanoparticlesrifampicinintracellular infection |
| spellingShingle | Manasi Jambhrunkar Sajedeh Maghrebi Divya Doddakyathanahalli Anthony Wignall Clive A. Prestidge Kristen E. Bremmell Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages Pharmaceutics antibacterial mesoporous silica nanoparticles rifampicin intracellular infection |
| title | Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages |
| title_full | Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages |
| title_fullStr | Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages |
| title_full_unstemmed | Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages |
| title_short | Mesoporous Organosilica Nanoparticles to Fight Intracellular Staphylococcal Aureus Infections in Macrophages |
| title_sort | mesoporous organosilica nanoparticles to fight intracellular staphylococcal aureus infections in macrophages |
| topic | antibacterial mesoporous silica nanoparticles rifampicin intracellular infection |
| url | https://www.mdpi.com/1999-4923/15/4/1037 |
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