Show simple item record

dc.contributor.authorObuobi, Sybil Akua Okyerewa
dc.contributor.authorJulin, Kjersti
dc.contributor.authorFredheim, Elizabeth G. Aarag
dc.contributor.authorJohannessen, Mona
dc.contributor.authorSkalko-Basnet, Natasa
dc.date.accessioned2021-03-09T07:56:39Z
dc.date.available2021-03-09T07:56:39Z
dc.date.issued2020-06-07
dc.description.abstractThe persistence of <i>Staphylococcus aureus</i> has been accredited to its ability to escape immune response via host cell invasion. Despite the efficacy of many antibiotics against <i>S. aureus</i>, the high extracellular concentrations of conventional antibiotics required for bactericidal activity is limited by their low cellular accumulation and poor intracellular retention. While nanocarriers have received tremendous attention for antibiotic delivery against persistent pathogens, they suffer daunting challenges such as low drug loading, poor retention and untimely release of hydrophilic cargos. Here, a hybrid system (Van_DNL) is fabricated wherein nucleic acid nanogels are caged within a liposomal vesicle for antibiotic delivery. The central principle of this approach relies on exploiting non-covalent electrostatic interactions between cationic cargos and polyanionic DNA to immobilize antibiotics and enable precise temporal release against intracellular <i>S. aureus. In vitro</i> characterization of Van_DNL revealed a stable homogenous formulation with circular morphology and enhanced vancomycin loading efficiency. The hybrid system significantly sustained the release of vancomycin over 24 h compared to liposomal or nanogel controls. Under enzymatic conditions relevant to <i>S. aureus</i> infections, lipase triggered release of vancomycin was observed from the hybrid. While using Van_DNL to treat <i>S. aureus</i> infected macrophages, a dose dependent reduction in intracellular bacterial load was observed over 24 h and exposure to Van_DNL for 48 h caused negligible cellular toxicity. Pre-treatment of macrophages with the antimicrobial hybrid resulted in a strong anti-inflammatory activity in synergy with vancomycin following endotoxin stimulation. Conceptually, these findings highlight these hybrids as a unique and universal platform for synergistic antimicrobial and anti-inflammatory therapy against persistent infections.en_US
dc.identifier.citationObuobi SAO, Julin K, Fredheim E, Johannessen M, Skalko-Basnet N. Liposomal delivery of antibiotic loaded nucleic acid nanogels with enhanced drug loading and synergistic anti-inflammatory activity against S. aureus intracellular infections. Journal of Controlled Release. 2020;324:620-632en_US
dc.identifier.cristinIDFRIDAID 1815925
dc.identifier.doi10.1016/j.jconrel.2020.06.002
dc.identifier.issn0168-3659
dc.identifier.issn1873-4995
dc.identifier.urihttps://hdl.handle.net/10037/20652
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of Controlled Release
dc.relation.projectIDEU: Marie Skłodowska-Curie grant agreement No 834811.en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/834811/EU/DNA nanohydrogel loaded Liposomal formulations for high loading efficiency of antimicrobial drugs against intracellular bacterial and topical biofilm infections/NANOZID/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Pharmacology: 728en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728en_US
dc.titleLiposomal delivery of antibiotic loaded nucleic acid nanogels with enhanced drug loading and synergistic anti-inflammatory activity against S. aureus intracellular infectionsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record