Renal-Targeted Drug Delivery by Chitosan Oligosaccharide Micelles with HSA-Enriched Protein Corona for the Treatment of Ischemia/Reperfusion-Induced Acute Kidney Injury.
ACS Appl Mater Interfaces
; 16(37): 49913-49925, 2024 Sep 18.
Article
in En
| MEDLINE
| ID: mdl-39240782
ABSTRACT
Renal-specific nanoparticulate drug delivery systems have shown great potential in reducing systemic side effects and improving the safety and efficacy of treatments for renal diseases. Here, stearic acid-grafted chitosan oligosaccharide (COS-SA) was synthesized as a renal-targeted carrier due to the high affinity of the 2-glucosamine moiety on COS to the megalin receptor expressed on renal proximal tubular epithelial cells. Specifically, COS-SA/CLT micelles were prepared by encapsulating celastrol (CLT) with COS-SA, and different proportions of human serum albumin (HSA) were then adsorbed onto its surface to explore the interaction between the protein corona and cationic polymeric micelles. Our results showed that a multilayered protein corona, consisting of an inner "hard" corona and an outer "soft" corona, was formed on the surface of COS-SA/CLT@HSA8, which was beneficial in preventing its recognition and phagocytosis by macrophages. The formation of HSA protein corona on COS-SA/CLT micelles also increased its accumulation in the renal tubules. Furthermore, the electropositivity of COS-SA/CLT micelles affected the conformation of adsorbed proteins to various degrees. During the adsorption process, the protein corona on the surface of COS-SA/CLT@HSA1 was partially denatured. Overall, COS-SA/CLT and COS-SA/CLT@HSA micelles demonstrated sufficient safety with renal targeting potential, providing a viable strategy for the management of ischemia/reperfusion-induced acute kidney injury.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligosaccharides
/
Reperfusion Injury
/
Chitosan
/
Acute Kidney Injury
/
Protein Corona
/
Serum Albumin, Human
/
Micelles
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
ACS Appl Mater Interfaces
Journal subject:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos