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An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance
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An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance
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Journal Article
An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Anti-Bacterial Agents - pharmacology
/ Drug Resistance, Bacterial - drug effects
/ High-performance liquid chromatography
/ Humanities and Social Sciences
/ Intracellular Space - metabolism
/ Mice
/ Microbial Viability - drug effects
/ Nanoparticles - ultrastructure
/ Prodrugs
/ Science
/ Staphylococcus aureus - drug effects
/ Staphylococcus aureus - growth & development
/ Terpenes
