Abstract: FR-PO993
Kidney-Specific Targeting Using PLGA Nanoparticles in Polycystic Kidney Disease Mice
Session Information
- PKD Cellular Pathogenesis, ARPKD, ADTKD, Ciliopathies
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidney
- 1001 Genetic Diseases of the Kidney: Cystic
Authors
- Oduk, Yasin, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Huang, Jifeng, University of Alabama at Birmingham, Birmingham, Alabama, United States
- He, Lan, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Saigusa, Takamitsu, University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Drugs that slow cystogenesis in murine models may not show similar results in clinical trials, possibly due to the smaller dose used in humans to avoid systemic side effects. One way to improve the efficiency of the drugs in the kidney, without increasing the drug dose/risk for adverse effects, is kidney-specific drug delivery. Polymeric nanoparticles (NP) can encapsulate drugs and they are small enough in size which can freely filter through the glomerulus and be reabsorbed in the tubules, without potentially being taken up by extra-renal organs. The purpose of this study is to determine the bio distribution of NP in polycystic kidney disease (PKD) mouse.
Methods
Fluorescent coumarin-6 encapsulated poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer nanoparticles were prepared by a double emulsion method with an average size of 124 ± 26nm, confirmed by scanning electron microscopy (SEM). PLGA-NP was administered via tail vein injection at the concentration of 50mg/kg to adult Pkd1 mice with moderate kidney cyst formation and control mice with no kidney cyst. Mice were sacrificed at 1, 4, 24, 48 and 72 hours after injection. Kidney, liver, heart, lung, and spleen were harvested and fixed for immunofluorescence and transmission electron microscopy (EM).
Results
Kidneys from both PKD and control mice revealed strong green fluorescent staining in the proximal tubules and in the arterial endothelium at 1 to 4 hour after injection, retaining its fluorescence at 24 hours and fading at 72 hours. There was PLGA-NP uptake in kidney cystic structures for both proximal and distal tubular cysts. PLGA NPs were present in the liver, heart, lung, and spleen early after the NP injections (1 to 4 hours) but diminished over time. The overall intensity of NP's in the extrarenal organs were significantly lower compared to the kidney. EM of kidney harvested at 24 hours revealed an intact NP structure in the cytosolic compartment of the tubular epithelium.
Conclusion
PLGA-NP in PKD mice were predominantly reabsorbed in the kidney tubules and cystic epithelia compared to extra-renal organs including the liver. PLGA-NP may have a role in kidney-specific drug delivery in PKD.
Funding
- NIDDK Support