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Kidney Week

Abstract: TH-OR040

Transdermal Delivery of Kidney-Targeting Nanoparticles

Session Information

  • Bioengineering
    November 07, 2019 | Location: 146 A/B, Walter E. Washington Convention Center
    Abstract Time: 06:18 PM - 06:30 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Tripathy, Nirmalya, University of Southern California, Los Angeles, California, United States
  • Chung, Eun ji, University of Southern California, Los Angeles, California, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation and kidney enlargement, resulting in end-stage renal failure. Most available therapies offer only controlling secondary consequences of ADPKD and are systemically administered via oral/intravenous routes in which drugs are eliminated by first pass metabolism, degraded by gastrointestinal tract, and cause off-target side effects. Herein, we aim to engineer a transdermal patch containing ADPKD treatment by combining 1) a dissolvable microneedle (DM) patch allowing controlled transdermal delivery of 2) kidney-targeted nanoparticles (KNP) with ADPKD-specific drugs. We hypothesize these KNP can deliver drugs specifically to diseased renal cells, thereby limiting systemic side effects while enhancing kidney bioavailability.

Methods

KNP were synthesized by self-assembly of DSPE-PEG(2000)-methoxy:DSPE-PEG(2000)-Folate:DSPE-PEG(2000)-FITC in 70:20:10 mol ratio and non-targeting NP consists of DSPE-PEG(2000)-methoxy:DSPE-PEG(2000)-FITC in 10:90 mol ratio. NP were studied by transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential. In vitro biocompatibility and binding were evaluated using MTS assay and confocal microscopy on human renal proximal tubule epithelial cells (RPTECs). The KNP incorporated DM (polyvinyl alcohol) patches were fabricated via micro-molding technique, evaluated for dissolution and NP release.

Results

Non-targeting and KNP exhibit a diameter of 15.0 ± 0.0 and 12.6 ± 1.2 nm as confirmed by TEM and DLS, and zeta potentials were found to be neutral (0.07 ± 0.2 and –0.32 ± 0.5 mV, respectively). When NP (1-100 μM) biocompatibility were assessed after 24 h on RPTECs, over 90% of cells were found to be viable and were comparable to the PBS-treated group. Additionally, KNP (100 μM) shown an enhanced binding as compared to non-targeting NP after 30 min. KNP incorporated DM patches consists of uniform microneedles of 600 µM height and 300 µM width. These patches showed complete dissolution within 120 ± 30 seconds in PBS at physiological pH 7.4, indicating potential for rapid transdermal release of NP.

Conclusion

Our transdermal delivery strategy of KNP offer a promising drug delivery system for ADPKD. Future studies will incorporate a library of drugs to test therapeutic efficacy in vivo.