Improving Antibacterial Activity of a HtrA Protease Inhibitor JO146 against Helicobacter pylori : A Novel Approach Using Microfluidics-Engineered PLGA Nanoparticles.
Jimin HwangSonya MrosAllan B GambleJoel D A TyndallArlene McDowellPublished in: Pharmaceutics (2022)
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 Helicobacter pylori 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- co -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 H. pylori compared to the free drug alone, highlighting that controlled engineering of nanoparticle size is important in drug delivery optimization.
Keyphrases
- helicobacter pylori
- drug delivery
- cancer therapy
- helicobacter pylori infection
- staphylococcus aureus
- high temperature
- iron oxide
- single cell
- drug release
- machine learning
- pseudomonas aeruginosa
- high throughput
- escherichia coli
- photodynamic therapy
- emergency department
- induced apoptosis
- genome wide
- small molecule
- silver nanoparticles
- cystic fibrosis
- wound healing
- circulating tumor cells
- cell death
- deep learning
- amino acid
- label free
- binding protein