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Transdermal Delivery of Kidney-Targeting Nanoparticles Using Dissolvable Microneedles
Nirmalya Tripathy1, Jonathan Wang1, Madelynn Tung1
1Department of Biomedical Engineering, University of Southern California, Los Angeles, CA USA.
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.
Insights
Kidney-targeted nanoparticles delivered via transdermal microneedles offer a promising, non-invasive treatment for chronic kidney disease. This novel approach enhances drug accumulation in the kidneys while preserving overall kidney health.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Nephrology
Background:
- Chronic kidney disease (CKD) affects 13% of the global population, often necessitating dialysis or transplantation.
- Current CKD drugs have limited efficacy and significant side effects.
- There is a critical need for targeted drug delivery systems with improved kidney specificity and patient-compliant administration routes.
Purpose of the Study:
- To explore kidney-targeted nanoparticles delivered via transdermal microneedles (KNP/MN) as a novel therapeutic strategy for CKD.
- To evaluate the biocompatibility, kidney targeting, and safety of the KNP/MN system.
Main Methods:
- Developed folate-conjugated micelle nanoparticles (KNP) incorporated into polyvinyl alcohol microneedle (MN) patches.
- Encapsulated Rhodamine B as a model drug in KNP for in vitro and in vivo evaluation.
- Assessed skin penetration, nanoparticle biocompatibility, folate receptor binding, biodistribution, organ morphology, and kidney function in mice.
Main Results:
- KNP demonstrated high biocompatibility and folate-dependent binding in vitro.
- Transdermal KNP/MN patches dissolved within 30 minutes, showing efficient skin penetration.
- In vivo studies revealed higher KNP accumulation in kidneys compared to control nanoparticles, with no observed tissue damage or adverse effects on kidney function markers.
Conclusions:
- KNP/MN patches show significant potential as a non-invasive, self-administrable platform for targeted kidney therapy.
- This approach could improve treatment efficacy and patient compliance for chronic kidney disease.
- Further development of KNP/MN systems may offer a new avenue for managing CKD.
