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Direct Drug Delivery to Kidney via the Renal Artery
Published on: April 17, 2021
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A kidney-selective biopolymer for targeted drug delivery
Gene L Bidwell1,2, Fakhri Mahdi3, Qingmei Shao3
1Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi; gbidwell@umc.edu.
American Journal of Physiology. Renal Physiology
|October 28, 2016
Summary
A novel kidney-targeting construct, KTP-ELP, enhances drug delivery specifically to the kidneys. This protein-based carrier shows high renal accumulation and no acute toxicity, paving the way for targeted renal disease treatments.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Nephrology
Background:
- Targeted drug delivery to the kidney remains an underdeveloped area for treating renal diseases.
- Elastin-like polypeptides (ELPs) are promising nonimmunogenic protein carriers for therapeutic stabilization.
Purpose of the Study:
- To develop and evaluate a kidney-targeting construct (KTP-ELP) for enhanced renal-specific drug delivery.
- To assess the in vivo pharmacokinetics, biodistribution, and safety of KTP-ELP.
Main Methods:
- Modification of ELP with a kidney-targeting peptide (KTP) and a cysteine residue.
- In vivo pharmacokinetic and biodistribution studies in rat and swine models.
- In vitro cell binding assays using human renal cells and assessment of renal toxicity.
Main Results:
- KTP-ELP exhibited a longer plasma half-life and fivefold higher kidney accumulation than untargeted ELP.
- Renal levels of KTP-ELP were 15- to over 150-fold higher than in other organs, with high accumulation in proximal tubules and vascular endothelium.
- No adverse effects on body weight, glomerular filtration rate, albuminuria, or renal tissue damage were observed after 14-day infusion.
Conclusions:
- KTP-ELP demonstrates high renal selectivity and is not species-specific.
- The construct shows no acute renal toxicity, supporting its potential for targeted renal therapies.
- ELP technology offers a versatile platform for developing targeted treatments for various renal diseases.
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