There is increasingly keen interest in developing orally delivered targeted drugs, especially for diseases that require long-term medication. Hence, we manufactured nanoparticles derived from methoxypolyethylene glycol-chitosan (PCS) to enhance the oral delivery and kidney-targeted distribution of salvianolic acid B (SalB), a naturally occurring renoprotective and anti-fibrotic compound, as a model drug for the treatment of renal fibrosis. Orally administered SalB-loaded PCS nanoparticles (SalB-PCS-NPs) maintained good stability in the gastrointestinal environment, improved mucus-penetrating capacity, and enhanced transmembrane transport through a Caco-2 cell monolayer. The relative oral bioavailability of SalB-PCS-NPs to free SalB and SalB-loaded chitosan nanoparticles (SalB-CS-NPs) was 367.0 % and 206.2 %, respectively. The structural integrity of SalB-PCS-NPs after crossing the intestinal barrier was also validated by Förster resonance energy transfer (FRET) in vitro and in vivo. Fluorescein isothiocyanate (FITC)-labeled SalB-PCS-NPs showed higher kidney accumulation than free FITC and FITC-labeled SalB-CS-NPs (4.6-fold and 2.1-fold, respectively). Significant improvements in kidney function, extracellular matrix accumulation, and pathological changes were observed in a unilateral ureter obstruction mouse model of renal fibrosis after once daily oral treatment with SalB-PCS-NPs for 14 days. Thus, oral administration of SalB-PCS-NPs represents a promising new strategy for kidney-targeted drug delivery.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijbiomac.2023.128315 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Serum amyloid P (PTX2) attenuates hepatic fibrosis in mice by inhibiting the activation of fibrocytes and HSCs.
Hepatol Commun
November 2024
Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Background: Liver fibrosis is caused by chronic toxic or cholestatic liver injury. Fibrosis results from the recruitment of myeloid cells into the injured liver, the release of inflammatory and fibrogenic cytokines, and the activation of myofibroblasts, which secrete extracellular matrix, mostly collagen type I. Hepatic myofibroblasts originate from liver-resident mesenchymal cells, including HSCs and bone marrow-derived CD45+ collagen type I+ expressing fibrocytes.
View Article and Find Full Text PDFCircadian clock gene BMAL1 is involved in transforming growth factor β1-induced fibrotic response in NRK-49F cells.
Cell Biol Int
January 2025
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Teine-ku, Japan.
The transcription factor brain and muscle Arnt-like protein-1 (BMAL1) is a clock protein involved in various diseases, including atherosclerosis and cancer. However, BMAL1's involvement in kidney fibrosis and the underlying mechanisms remain largely unknown, a gap addressed in this study. Analysis through Masson's trichrome and Sirius red staining revealed that all groups exposed to unilateral ureteral obstruction showed increased BMAL1 protein expression accompanied by increased TGF-β1 expression and elevated key fibrosis markers, including α-SMA, compared with sham groups.
View Article and Find Full Text PDFThe Long-Range Chromosomal Interaction Controlling Klotho Gene Expression in Human Chronic Kidney Disease.
ACS Omega
December 2024
Department of Urology, Suzhou Ninth Hospital affiliated to Soochow University, Suzhou 215000, China.
Cis-regulatory elements bridge enhancers and gene promoters to control gene expression via distal DNA interaction and three-dimensional chromosomal conformation organization. The aberrant changes of cis-acting regulatory systems as one type of the epigenetic regulative ways may be connected with human genetic diseases. Klotho, as an antiaging protein, is selectively expressed in kidney tissues and plays a crucial role in preventing chronic kidney disease (CKD) and renal fibrosis.
View Article and Find Full Text PDFBone Marrow Mesenchymal Stem Cells Ameliorate Diabetes and Diabetic Renal Fibrosis by Modulating the Inflammatory Factor IL-11.
Curr Stem Cell Res Ther
December 2024
Department of Nephrology, The Second Hospital Affiliated to Kunming Medical University, Kunming, 650101, China.
Objective: This study aims to explore the therapeutic potential of mesenchymal stem cells (MSC) in treating diabetic nephropathy (DN) by investigating their effect on IL-11 modulation in a mouse model.
Methods: The effects of MSC therapy on DN were examined both in vivo and in vitro. Sixty adult male C57BL/6 mice were divided into the streptozotocin (STZ) diabetes (T1D) and the high-fat diet diabetes (T2D) models, with both groups receiving MSC treatment or saline for 4 or 8 weeks.
Deep learning-based histopathological assessment of tubulo-interstitial injury in chronic kidney diseases.
Commun Med (Lond)
January 2025
Department of Dermatology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Background: Chronic kidney disease (CKD) causes progressive and irreversible damage to the kidneys. Renal biopsies are essential for diagnosing the etiology and prognosis of CKD, while accurate quantification of tubulo-interstitial injuries from whole slide images (WSIs) of renal biopsy specimens is challenging with visual inspection alone.
Methods: We develop a deep learning-based method named DLRS to quantify interstitial fibrosis and inflammatory cell infiltration as tubulo-interstitial injury scores, from WSIs of renal biopsy specimens.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!