title: PEGylated ofloxacin nanoparticles render strong antibacterial activity against many clinically important human pathogens.
abstract: The rise of bacterial resistance against important drugs threatens their clinical utility. Fluoroquinones, one of the most important classes of contemporary antibiotics has also reported to suffer bacterial resistance. Since the general mechanism of bacterial resistance against fluoroquinone antibiotics (e.g. ofloxacin) consists of target mutations resulting in reduced membrane permeability and increased efflux by the bacteria, strategies that could increase bacterial uptake and reduce efflux of the drug would provide effective treatment. In the present study, we have compared the efficiencies of ofloxacin delivered in the form of free drug (OFX) and as nanoparticles on bacterial uptake and antibacterial activity. Although both poly(lactic-co-glycolic acid) (OFX-PLGA) and methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (OFX-mPEG-PLGA) nanoformulations presented improved bacterial uptake and antibacterial activity against all the tested human bacterial pathogens, namely, Escherichia coli, Proteus vulgaris, Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus, OFX-mPEG-PLGA showed significantly higher bacterial uptake and antibacterial activity compared to OFX-PLGA. We have also found that mPEG-PLGA nanoencapsulation could significantly inhibit Bacillus subtilis resistance development against OFX.
authors.affiliation: Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Portugal.
authors.forename: Gregory
authors.initials: G
authors.lastname: Marslin
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Ann Mary
authors.initials: AM
authors.lastname: Revina
authors.affiliation: Consorzio Mario Negri Sud, Department of Translational Pharmacology, Santa Maria Imbaro, Italy.
authors.forename: Vinoth Kumar Megraj
authors.initials: VK
authors.lastname: Khandelwal
authors.affiliation: Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamilnadu, India.
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Balakumar
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Faro, Portugal; IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Faro, Portugal.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Sheeba
authors.affiliation: Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Portugal. Electronic address: franklin@bio.uminho.pt.
authors.forename: Gregory
authors.initials: G
authors.lastname: Franklin
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D015242:Ofloxacin / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D011092:Polyethylene Glycols; D015242:Ofloxacin
keywords: Antibacterial; Antibiotic resistance; Bacterial uptake; Nanoparticles; Ofloxacin; mPEG-PLGA diblock Co-polymer