Improving Antibacterial Activity of a HtrA Protease Inhibitor JO146 against Helicobacter pylori : A Novel Approach Using Microfluidics-Engineered PLGA Nanoparticles

Nanoparticle drug delivery systems have emerged as a promising strategy for overcoming limitations of antimicrobial drugs such as stability, bioavailability, and insufficient exposure to the hard-to-reach bacterial drug targets. Although size is a vital colloidal feature of nanoparticles that govern...

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Bibliographic Details
Published in:Pharmaceutics 2022-02, Vol.14 (2), p.348
Main Authors: Hwang, Jimin, Mros, Sonya, Gamble, Allan B, Tyndall, Joel D A, McDowell, Arlene
Format: Article
Language:English
Subjects:
Antibiotics
Bacteria
Bacterial infections
Biodistribution
Chlamydia
Design of experiments
Drug resistance
E coli
Gram-negative bacteria
H. pylori
Infections
Laboratories
microfluidics
Nanomaterials
Nanoparticles
Particle size
Pathogens
Peptides
poly(lactic-co-glycolic) acid
Polyvinyl alcohol
Proteins
size
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Summary:Nanoparticle drug delivery systems have emerged as a promising strategy for overcoming limitations of antimicrobial drugs such as stability, bioavailability, and insufficient exposure to the hard-to-reach bacterial drug targets. Although size is a vital colloidal feature of nanoparticles that governs biological interactions, the absence of well-defined size control technology has hampered the investigation of optimal nanoparticle size for targeting bacterial cells. Previously, we identified a lead antichlamydial compound JO146 against the high temperature requirement A (HtrA) protease, a promising antibacterial target involved in protein quality control and virulence. Here, we reveal that JO146 was active against with a minimum bactericidal concentration of 18.8-75.2 µg/mL. Microfluidic technology using a design of experiments approach was utilized to formulate JO146-loaded poly(lactic- -glycolic) acid nanoparticles and explore the effect of the nanoparticle size on drug delivery. JO146-loaded nanoparticles of three different sizes (90, 150, and 220 nm) were formulated with uniform particle size distribution and drug encapsulation efficiency of up to 25%. In in vitro microdilution inhibition assays, 90 nm nanoparticles improved the minimum bactericidal concentration of JO146 two-fold against compared to the free drug alone, highlighting that controlled engineering of nanoparticle size is important in drug delivery optimization.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14020348