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Enhanced design and formulation of nanoparticles for anti-biofilm drug delivery

Authors
 Kenneth R. Sims  ;  Yuan Liu  ;  Geelsu Hwang  ;  Hoi In Jung  ;  Hyun Koo  ;  Danielle S. W. Benoit 
Citation
 NANOSCALE, Vol.11(1) : 219-236, 2018 
Journal Title
 NANOSCALE 
ISSN
 2040-3364 
Issue Date
2018
Abstract
Biofilms are surface-bound, structured microbial communities underpinning persistent bacterial infections. Biofilms often create acidic pH microenvironments, providing opportunities to leverage responsive drug delivery systems to improve antibacterial efficacy. Here, the antibacterial efficacy of novel formulations containing pH-responsive polymer nanoparticle carriers (NPCs) and farnesol, a hydrophobic antibacterial drug, were investigated. Multiple farnesol-loaded NPCs, which varied in overall molecular weight and corona-to-core molecular weight ratios (CCRs), were tested using standard and saturated drug loading conditions. NPCs loaded at saturated conditions exhibited ∼300% greater drug loading capacity over standard conditions. Furthermore, saturated loading conditions sustained zero-ordered drug release over 48 hours, which was 3-fold longer than using standard farnesol loading. Anti-biofilm activity of saturated NPC loading was markedly amplified using Streptococcus mutans as a biofilm-forming model organism. Specifically, reductions of ∼2-4 log colony forming unit (CFU) were obtained using microplate and saliva-coated hydroxyapatite biofilm assays. Mechanistically, the new formulation reduced total biomass by disrupting insoluble glucan formation and increased NPC-cell membrane localization. Finally, thonzonium bromide, a highly potent, FDA-approved antibacterial drug with similar alkyl chain structure to farnesol, was also loaded into NPCs and used to treat S. mutans biofilms. Similar to farnesol-loaded NPCs, thonzonium bromide-loaded NPCs increased drug loading capacity ≥2.5-fold, demonstrated nearly zero-order release kinetics over 96 hours, and reduced biofilm cell viability by ∼6 log CFU. This work provides foundational insights that may lead to clinical translation of novel topical biofilm-targeting therapies, such as those for oral diseases.
Full Text
https://pubs.rsc.org/en/Content/ArticleLanding/2019/NR/C8NR05784B#!divAbstract
DOI
10.1039/c8nr05784b
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Preventive Dentistry and Public Oral Health (예방치과학교실) > 1. Journal Papers
Yonsei Authors
Jung, Hoi In(정회인) ORCID logo https://orcid.org/0000-0002-1978-6926
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167182
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