An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance
| Autor: | Ruxandra Gref, Julie Mougin, Fatouma Saïd-Hassane, Fatima Zouhiri, Nadia Abed, Valérie Nicolas, Didier Desmaële, Patrick Couvreur |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Drug
Staphylococcus aureus medicine.drug_class media_common.quotation_subject Antibiotics Intracellular Space Microbial Sensitivity Tests 02 engineering and technology Drug resistance Biology beta-Lactams medicine.disease_cause Article Microbiology Mice 03 medical and health sciences Drug Delivery Systems Antibiotic resistance Drug Resistance Bacterial medicine Animals 030304 developmental biology media_common 0303 health sciences Microbial Viability Multidisciplinary Cell Death Penicillin G Prodrug 021001 nanoscience & nanotechnology Endocytosis Anti-Bacterial Agents Penicillin RAW 264.7 Cells Nanoparticles 0210 nano-technology Intracellular medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep13500 |
| Popis: | The “Golden era” of antibiotics is definitely an old story and this is especially true for intracellular bacterial infections. The poor intracellular bioavailability of antibiotics reduces the efficency of many treatments and thereby promotes resistances. Therefore, the development of nanodevices coupled with antibiotics that are capable of targeting and releasing the drug into the infected-cells appears to be a promising solution to circumvent these complications. Here, we took advantage of two natural terpenes (farnesyl and geranyl) to design nanodevices for an efficient intracellular delivery of penicillin G. The covalent linkage between the terpene moieties and the antibiotic leads to formation of prodrugs that self-assemble to form nanoparticles with a high drug payload between 55–63%. Futhermore, the addition of an environmentally-sensitive bond between the antibiotic and the terpene led to an efficient antibacterial activity against the intracellular pathogen Staphylococcus aureus with reduced intracellular replication of about 99.9% compared to untreated infected cells. Using HPLC analysis, we demonstrated and quantified the intracellular release of PenG when this sensitive-bond (SB) was present on the prodrug, showing the success of this technology to deliver antibiotics directly into cells. |
| Databáze: | OpenAIRE |
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