Targeting Kidney Fibrosis

Targeted delivery systems represent a promising technology to improve drug efficacy and safety in the treatment of diseases. Its advantages include convenience in administration, noninvasive, accurate dose, higher compliance and economical. With abundant experience in targeted delivery systems development, Creative Biolabs provides a full range of targeted delivery services for kidney fibrosis. Our professional team is optimized to help you with high-quality and cost-effective service to make your project a success.

Kidney Fibrosis

The incidence of chronic kidney disease (CKD) has been steadily increasing for the past 2 decades, and an estimated 31 million people in the United States have CKD. Moreover, the incidence of end-stage renal disease has climbed to a rate of 350 per million in the US population. Renal fibrosis is a direct result of the kidney's limited capacity to regenerate after injury. Renal scarring leads to a progressive loss of renal function, ultimately causing end-stage renal failure and a requirement for dialysis or kidney transplantation. Renal fibrosis presents an increase in the extracellular matrix and can be caused by a de novo synthesis of matrix (primarily collagen), or a disproportionate loss of renal parenchyma. In both cases, the process relies on a resident mesenchymal cell, i.e. myofibroblast, and is independent of disease etiology. Currently, it is urgent not only new drugs development for renal disease, but also new strategies to improve drug delivery to the kidney and target therapeutics to the appropriate cell type.

Fig.1 Mechanism of renal fibrosis.¹

Delivery System Targeting Kidney Fibrosis

Using renal-targeted therapeutics to improve drug delivery to the kidney is a promising method. Previous studies focused on kidney-selective drug delivery by utilizing passive targeting of endogenous low-molecular weight proteins that naturally accumulate in kidney, such as lysozyme, immunoglobulin light chain, or insulin. However, this strategy may be limited since these proteins tend to be filtered and taken up by tubular cells. Potential alternatives include utilizing glycoconjugates to target drugs to specific renal membrane receptors or linking therapeutics to nanoparticle carriers that are too large to be filtered, which may target pre- and glomerular cells. Other approaches for renal targeting can be achieved by fusing drugs to ligands for receptors overexpressed in kidney, such as a galectin-3 targeting peptide, that has been tested for renally targeted delivery of captopril.

Fig.2 CeNP-PEG reverses the renal fibrosis by blocking the dysregulated metabolic status, in which OXPHOS switches to the aerobic glycolytic program.²

Recently, a novel kidney-targeted construct for renal-specific drug delivery has been developed. Elastin-like polypeptides (ELPs) are non-immunogenic protein-based carriers that can stabilize attached small-molecule and peptide therapeutics. ELP was modified at its NH₂-terminus with a cyclic, seven-amino acid kidney-targeting peptide (KTP) and at its COOH-terminus with a cysteine residue for tracer conjugation. Comparative in vivo pharmacokinetics and biodistribution and in vitro cell binding studies demonstrated that KTP-ELP has a longer plasma half-life than ELP in kidneys at levels five-fold higher than untargeted ELP, showing renal levels 15- to over 150-fold higher than in other major organs. Renal fluorescence histology showed a high accumulation of KTP-ELP in proximal tubules and vascular endothelium. Furthermore, a high dose of ELP or KTP-ELP did not cause renal tissue damage compared to controls. These results suggest the high renal selectivity of KTP-ELP and demonstrate that it does not induce acute renal toxicity. The ELP technology for the targeted treatment of renal disease displays a promising application.

What Can We Do for You?

Targeted delivery of drugs represents a significant advance in disease diagnosis and therapy. Therefore, the development of novel target-specific ligands or pharmaceutical nanocarriers is highly desirable. Over the past decades, Creative Biolabs has built many module delivery systems for the development of targeted delivery system. The high-affinity and high-specificity targeted delivery technology for disease treatment have been established. If you are interested in our service, please do not hesitate to contact us for more details.

References

1. Zhang, Yuqing, et al. "Signaling pathways involved in diabetic renal fibrosis." Frontiers in cell and developmental biology 9 (2021): 696542.
2. Wang, Mengling, et al. "Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis." Journal of nanobiotechnology 20 (2022): 1-18.

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