Abstract

AbstractThe aim of this study is to explore the kidney-targeting capability of mesoscale nanoparticles (MNPs)-emodin (Em-MNPs) and its potential antifibrosis in the animal model. First, MNPs and Em-MNPs were synthesized via nanoprecipitation method, and their diameters were both ∼400 nm with the uniform size. The entrapment efficiency of MNPs was 45.1% when adding emodin at the concentration of 12 mg/mL. Moreover, cytotoxicity assay showed that Em-MNPs presented excellent biocompatibility in rat proximal tubular cells. Cellular uptake assay demonstrated that Em-MNPs had high-efficiency uptake, especially in the cytoplasm. Ex vivo organ fluorescence imaging revealed that Em-MNPs possessed specific kidney-targeting ability with relative long retention time in the kidney (∼24 h). In the renal unilateral ureteral obstruction model, Em-MNPs treatment could significantly alleviate kidney tubule injury and reduce extracellular matrix deposition compared with free MNPs. Herein, Em-MNPs with specific kidney-targeting and preferable antifibrosis effects in animal model may pave an avenue for treating renal diseases.

Highlights

  • Multifunctional nanomaterials have been widely studied in the biomedical field because of their unique and adjustable physicochemical properties [1]

  • Before hydrodynamic diameter (HD) of Em-mesoscale nanoparticles (MNPs) was determined, the phosphate buffered solution (PBS) and saline dispersions of Em-MNPs were diluted with 2 mL water, and the Fetal bovine serum (FBS) dispersions of Em-MNPs were centrifuged (6,600 rpm, 15 min) to remove FBS, and 2 mL water was added for dispersion

  • The structures of PLGA-b-mPEG and the encapsulation of Em were confirmed by 1H nuclear magnetic resonance spectra, Fourier transform infrared (FTIR) and UV-vis spectra

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Summary

Introduction

Multifunctional nanomaterials have been widely studied in the biomedical field because of their unique and adjustable physicochemical properties [1] Researches focused on their application in biosensor, bioimaging and diagnosis, drug delivery, and disease treatment, and tissue regeneration engineering have attracted widespread attention [2–5]. (emodin and triptolide) that were verified have been useful in treating chronic kidney fibrosis [10–12] They have some disadvantages such as low aqueous solubility, low kidney targeting, and short retention that may limit their application [13]. Qiao et al synthesized catecholderived chitosan complex (HCA-Chi) to improve the water solubility and renal-targeting ability of emodin and to further alleviate chronic kidney injury, which was an effective way to increase the effects of Chinese herbs [16]. Em-MNPs with good biocompatibility, kidney-targeting ability, and high uptake efficiency of kidney cells were synthesized for further pharmacodynamics study. We revealed that Em-MNPs had good therapeutic effects in the renal fibrosis animal model

Chemicals
Fabrication of PLGA-b-mPEG
In vitro stability and drug release of Em-MNPs
Cell uptake assay
Cytotoxicity assay
Kidney targeting evaluation
Characterization of PLGA-b-mPEG and Em-MNPs
Optimization of the Em-MNPs fabrication
Stability and in vitro release assays
Cellular uptake study
Kidney targeting capacity
Conclusion
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