Transdermal Delivery of Kidney-Targeting Nanoparticles Using Dissolvable Microneedles

Abstract

Introduction

Chronic kidney disease (CKD) affects approximately 13% of the world’s population and will lead to dialysis or kidney transplantation. Unfortunately, clinically available drugs for CKD show limited efficacy and toxic extrarenal side effects. Hence, there is a need to develop targeted delivery systems with enhanced kidney specificity that can also be combined with a patient-compliant administration route for such patients that need extended treatment. Towards this goal, kidney-targeted nanoparticles administered through transdermal microneedles (KNP/MN) is explored in this study.

Methods

A KNP/MN patch was developed by incorporating folate-conjugated micelle nanoparticles into polyvinyl alcohol MN patches. Rhodamine B (RhB) was encapsulated into KNP as a model drug and evaluated for biocompatibility and binding with human renal epithelial cells. For MN, skin penetration efficiency was assessed using a Parafilm model, and penetration was imaged via scanning electron microscopy. In vivo, KNP/MN patches were applied on the backs of C57BL/6 wild type mice and biodistribution, organ morphology, and kidney function assessed.

Results

KNP showed high biocompatibility and folate-dependent binding in vitro, validating KNP’s targeting to folate receptors in vitro. Upon transdermal administration in vivo, KNP/MN patches dissolved within 30 min. At varying time points up to 48 h post-KNP/MN administration, higher accumulation of KNP was found in kidneys compared with MN that consisted of the non-targeting, control-NP. Histological evaluation demonstrated no signs of tissue damage, and kidney function markers, serum blood urea nitrogen and urine creatinine, were found to be within normal ranges, indicating preservation of kidney health.

Conclusions

Our studies show potential of KNP/MN patches as a non-invasive, self-administrable platform to direct therapies to the kidneys.

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Acknowledgments

The authors would like to acknowledge the financial support from the Women in Science and Engineering (WiSE), Gabilan Assistant Professorship, L. K. Whittier Foundation, the National Heart, Lung, and Blood Institute (NHLBI, R00HL124279), and NIH New Innovator Award (DP2-DK121328) awarded to EJC. TEM images were taken with the aid of the USC Center of Excellence in Nano Imaging.

Conflict of interest

Nirmalya Tripathy, Jonathan Wang, Madelynn Tung, Claire Conway, and Eun Ji Chung have no conflicts of interest to disclose.

Animal Studies

All animal studies followed NIH guidelines for the care and use of laboratory animals and were conducted and approved by the University of Southern California’s Institutional Animal Care and Use Committee (Los Angeles, CA, USA).

Human Studies

No human studies were carried out by the authors for this article.

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Tripathy, N., Wang, J., Tung, M. et al. Transdermal Delivery of Kidney-Targeting Nanoparticles Using Dissolvable Microneedles. Cel. Mol. Bioeng. (2020). https://doi.org/10.1007/s12195-020-00622-3

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Keywords

  • Chronic kidney disease
  • Kidney-targeting
  • Nanoparticles
  • Folate
  • Microneedles