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dc.contributor.authorTran, The-Thienen_US
dc.contributor.authorHadinoto, Kunnen_US
dc.identifier.citationTran, T. & Hadinoto, K. (2020). Ternary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapy. Colloids and Surfaces. B, Biointerfaces, 193, 111095-.
dc.description.abstractAntibiotic-polyelectrolyte nanoparticle complex (or nanoplex in short) has been recently demonstrated as a superior antibiotic delivery system to the native antibiotic in bronchiectasis therapy owed to its ability to overcome the lung's mucus barrier and generate high localized antibiotic exposure in the infected sites. The present work aimed to further improve the mucus permeability, hence the antibacterial efficacy of the nanoplex, by incorporating mucolytic enzyme papain (PAP) at the nanoplex formation step to produce PAP-decorated antibiotic-polyelectrolyte nanoplex exhibiting built-in mucolytic capability. Ciprofloxacin (CIP) and dextran sulfate (DXT) were used as the models for antibiotics and polyelectrolyte, respectively. The results showed that the PAP inclusion had minimal effects on the physical characteristics, preparation efficiency, and dissolution of the CIP-DXT nanoplex. The optimal CIP-(DXT-PAP) nanoplex exhibited size and zeta potential of approximately 200 nm and -50 mV with CIP and PAP payloads of 60% and 32% (w/w), respectively. The nanoplex was prepared at high efficiency with larger than 80% CIP and PAP utilization rates. The CIP-(DXT-PAP) nanoplex exhibited tenfold improvement in the mucus permeability compared to its CIP-DXT nanoplex counterpart, resulting in the former's superior bactericidal activity against clinical Pseudomonas aeruginosa biofilm in the presence of mucus barrier. A trade-off, nevertheless, existed between antibacterial efficacy and cytotoxicity towards human lung epithelium cells upon the incorporation of PAP above a certain concentration threshold. Therefore, the optimal dosing of the CIP-(DXT-PAP) nanoplex must be carefully determined.en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.relation.ispartofColloids and surfaces. B, Biointerfacesen_US
dc.rights© 2020 Elsevier B.V. All rights reserved.en_US
dc.titleTernary nanoparticle complex of antibiotic, polyelectrolyte, and mucolytic enzyme as a potential antibiotic delivery system in bronchiectasis therapyen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Chemical and Biomedical Engineeringen_US
dc.subject.keywordsDrug–Polyelectrolyte Complexen_US
dc.description.acknowledgementThis work was supported by LKCMedicine-SCBE Collaborative Grant (CG-04/16) from Nanyang Technological University Singapore.en_US
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