Optimizing Free Radical Scavenger-Loaded Kidney-Targeted Polymeric Nanoparticles for Increased Therapeutic Efficacy in CKD
- Bioengineering: Modeling, Diagnosis, Therapy
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
- 400 Bioengineering
- Vasylaki, Anastasiia, The City College of New York, New York, New York, United States
- Roach, Arantxa, The City College of New York, New York, New York, United States
- Ghosh, Pratyusha, The City College of New York, New York, New York, United States
- Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Williams, Ryan, The City College of New York, New York, New York, United States
Therapeutic development for renal diseases has been hampered by a lack of poor pharmacological properties by many investigational drugs. To alleviate this bottleneck, our prior studies discovered a polymeric mesoscale nanoparticle (MNP) system capable of targeting the kidneys, specifically the renal proximal tubules. Here, we sought to define MNP formulation characteristics such that the system is robust to delivery of a small molecule cargo while maintaining the appropriate surface chemistry and size necessary for renal targeting.
We used a quantitative statistical modelling approach based on the Design of Experiments (DoE) to define which drug and particle formulation characteristics allow for MNP renal targeting. We formulated MNPs with the FDA-approved ROS scavenger edaravone and a biocompatible, FDA-approved polymer made of poly(lactic-co-glycolic acid) coated with polyethylene glycol (PLGA-PEG).
We found that MNP formulation parameters control the ability to target the renal proximal tubules and modifications allow for robust production of MNPs with varying therapeutic cargoes. Specifically, polymer concentration and solvent ratios allow mesoscale formulation and optimization of drug cargo loading for therapeutic drug delivery to the kidney.
Ongoing studies are aimed at using these formulation parameters to incorporate increased therapeutic cargo and their ability to ameliorate hypertensive chronic kidney disease.
a) MNP localization to the kidneys in mice. b) MNPs (red) in mouse kidneys. C) Edaravone-loaded MNPs successfully ameliorate cisplatin-induced acute kidney injury. d) Contour plot from DoE indicating the appropriate formulation parameters to obtain kidney-targeted MNPS (in white).
- Other NIH Support