Hydrogel and nanoparticle carriers for kidney disease therapy: trends and recent advancements

Abstract

Achieving local therapeutic agent concentration in the kidneys through traditional systemic administration routes have associated concerns with off-target drug effects and toxicity. Additionally, kidney diseases are often accompanied by co-morbidities in other major organs, which negatively impacts drug metabolism and clearance. To circumvent these issues, kidney-specific targeting of therapeutics aims to achieve the delivery of controlled doses of therapeutic agents, such as drugs, nucleic acids, peptides, or proteins, to kidney tissues in a safe and efficient manner. Current carrier material approaches implement macromolecular and polyplex hydrogel constructs, prodrug strategies, and nanoparticle-based delivery technologies. In the context of multidisciplinary and cross-discipline innovations, the medical and bioengineering research fields have facilitated the rapid development of kidney-targeted therapies and carrier materials. In this review, we summarize the current trends and recent advancements made in the development of carrier materials for kidney disease targeted therapies, specifically hydrogel and nanoparticle-based strategies for acute kidney disease, chronic kidney disease, and renal cell carcinoma. Additionally, we discuss the current limitations in carrier materials and their delivery mechanisms.

Emergent Peptides of the Antifibrotic Arsenal: Taking Aim at Myofibroblast Promoting Pathways

“…Subsequent delivery to multiple models of hepatic fibrosis demonstrated the localized release of the cytotoxic mature melittin in response to elevated FAP production by activated hepatic stellate cells (aHSC), thereby inducing aHSC apoptosis, reducing collagen accumulation, and enabling liver recovery. The study also helps to underline the issues related to peptide therapies administered without carrier materials, as highlighted in a review by Gu et al [ 52 ], which provides a detailed account of the necessity for carrier materials to enhance kidney therapy efficacy. Much like drugs, the susceptibility of peptides to rapid degradation and unspecific uptake, whether by circulating cells or the cells of off-target organs, ultimately restricts efficacy and increases the risk of off-target effects and toxicity.…”

Targeting the Kidneys at the Nanoscale: Nanotechnology in Nephrology

“…Several papers have reviewed kidney-targeted treatments used for particular kidney conditions, including various etiologies of AKI and CKD, renal cell carcinoma, renal fibrosis, and other kidney diseases. 33 – 41 Another group of review articles has focused on nanomedicines targeting different parts of the nephron, 42 , 43 specific cell types, 37 , 39 , 44 , 45 and subcellular localization. 44 Kidney targeting has also been described in relation to different drug carrier types, such as antibody conjugates, small molecule prodrugs, protein and peptide carriers, polymeric carriers, and NPs.…”

Targeted glomerular mesangium transfection by antifibrotic gene nanocarriers inhibits kidney fibrosis and promotes regeneration

“…[39,40] Currently, there has been a great deal of attention focused on the design and evaluation of nanocarriers with elevated accumulation and e cacy for the treatment of kidney diseases. [33,39,[41][42][43] Nanoparticles provide multiple advantages that show promise in overcoming the limitations of traditional carriers in the treatment of many diseases. [33,44,45] However, the e caciousness of kidney-targeted and nanomaterial-based therapeutics remains variable amongst published studies, often hampered by the dominant uptake of nanoparticles from the circulating blood and into the liver, although this is rarely brought to attention.…”

“…Complicated by similar di culties faced by the traditional systemic routes of drug administration, an increased dosage, frequency of dosing, or combinatory drug synergism are required to achieve bioactive therapeutic concentration ranges of rhGFs in the kidneys, and this still does not guarantee effective delivery to key renal cell types. [33] The lack of speci city of drug and rhGF distribution may lead to systemic toxicity and off-target effects. [34] Thus, gene-carrier nanotechnologies have emerged as favorable solutions to achieving localized therapeutic levels of rhGFs, [35][36][37][38] and successful gene-based interventions have been demonstrated in kidney disease models in recent nonclinical studies.…”

“…[33,39,[41][42][43] Nanoparticles provide multiple advantages that show promise in overcoming the limitations of traditional carriers in the treatment of many diseases. [33,44,45] However, the e caciousness of kidney-targeted and nanomaterial-based therapeutics remains variable amongst published studies, often hampered by the dominant uptake of nanoparticles from the circulating blood and into the liver, although this is rarely brought to attention. Recent strategies have taken advantage of the inherent kidney-targeting properties of certain biomolecules to decorate carrier materials.…”