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Kidney Week

Abstract: PO1562

Oral Delivery of Nanoparticles for Renal Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Wang, Jonathan, University of Southern California, Los Angeles, California, United States
  • Hallows, Kenneth R., University of Southern California, Los Angeles, California, United States
  • Chung, Eun ji, University of Southern California, Los Angeles, California, United States
Background

Nanomaterials are promising for drug delivery, but few have been successful for oral delivery, the optimal route for chronic diseases like polycystic kidney disease (PKD). Drug candidates that slow cyst growth require high dosages leading to side effects like hepatoxicity. To limit this, we previously developed kidney targeting micelles (KM) and found they accumulated in the kidneys. To augment this system for oral delivery, herein, we load KMs and metformin (met), a diabetes drug with PKD promise, into chitosan nanocapsules (CS-NC) to overcome the barriers of the gastrointestinal (GI) tract. We hypothesize that CS-NC will deliver met across the GI tract and show efficacy in PKD mice models. Furthermore, we characterize KMs loaded into CS-NC to serve as a platform for future oral delivery of targeted therapeutics.

Methods

CS-NC were synthesized via ionic gelation. To confirm KM loading into CS-NC, dynamic light scattering (DLS) was performed for the following: KMs loaded into CS-NC, KMs mixed with CS-NC, CS-NC, or KM. To assess the oral delivery performance, we orally gavaged 300 mg/kg met loaded in CS-NC or free met to Pkd1fl/fl;Pax8 rtTA;Tet-O cre mice. On P22, kidneys were excised to assess kidney morphology.

Results

DLS of CS-NC showed diameters of 148.5 ± 0.3 nm , while KMs are 14.9 ± 1.5 nm (Fig. 1 Ai, ii). DLS results of the mixed conditions show both populations of particles (Fig. 1 Aiii), whereas loading KMs within CS-NCs removes free KMs (Fig. 1 Aiv), demonstrating encapsulation within CS-NCs. TEM of KMs (Fig. 1 B) and CS-NC (Fig. 1 C) show spherical morphology. Upon oral gavage of CS-NC met, a lower kidney to body weight ratio (10.3 ± 1.1 vs. 13.1 ± 1.0) and (b) cystic index (57.6 ± 1.2 vs. 66.5 ± 0.8) was seen in the CS-NC met group vs. free met (Fig. 1 E,F) (N ≥ 4, **p ≤ 0.01, ****p ≤ 0.0001).

Conclusion

These initial studies show promise that KMs can be loaded within CS-NCs and can function as an orally delivered targeted nanotherapeutic. To our knowledge, our studies represent the first nanomedicine strategy for PKD therapy.

Funding

  • Other NIH Support