Synthesis, physicochemical characterization, toxicity and efficacy of a PEG conjugate and a hybrid PEG conjugate nanoparticle formulation of the antibiotic moxifloxacin
| Autor: | Lesego Tshweu, Mohammed Balogun, Mervin Meyer, Nicole Remaliah Samantha Sibuyi, Admire Dube, Lynne A. Pilcher, Abdullah E. Gouda, Aya Abdelghany, Mohamed Shemis |
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| Rok vydání: | 2019 |
| Předmět: |
Chemistry
medicine.drug_class General Chemical Engineering Antibiotics technology industry and agriculture 02 engineering and technology General Chemistry Drug resistance Pharmacology 010402 general chemistry 021001 nanoscience & nanotechnology Antimicrobial 01 natural sciences 0104 chemical sciences Fluoroquinolone Antibiotic Moxifloxacin PEG ratio medicine 0210 nano-technology Antibacterial activity Conjugate medicine.drug |
| Zdroj: | RSC advances. 10(34) |
| ISSN: | 2046-2069 |
| Popis: | Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of treatment regimens which in turn leads to the development of drug resistance. We report on the development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing human cells. The broad-spectrum fluoroquinolone antibiotic moxifloxacin (Mox) was successfully conjugated to poly(ethylene glycol) (PEG) which was further encapsulated into the hydrophobic poly(e-caprolactone) (PCL) nanoparticles (NPs) with high efficiency, average particle size of 241.8 ± 4 nm and negative zeta potential. Toxicity against erythrocytes and MDBK cell lines and drug release in human plasma were evaluated. Hemocompatibility and reduced cytotoxicity of the PEG–Mox and PCL(PEG–Mox) NPs were demonstrated in comparison to free Mox. Antimicrobial activity was assessed against drug sensitive and resistant: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The antibacterial activity of Mox was largely maintained after conjugation. Our data shows that the toxicity of Mox can be effectively attenuated while, in the case of PEG–Mox, retaining significant antibacterial activity. At the conditions employed in this study for antimicrobial activity the encapsulated conjugate (PCL(PEG–Mox) NPs) did not demonstrate, conclusively, significant antibacterial activity. These systems do, however, hold promise if further developed for improved treatment of bacterial infections. |
| Databáze: | OpenAIRE |
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