Hyaluronic Acid-Functionalized Mesoporous Silica Nanoparticles Loading Simvastatin for Targeted Therapy of Atherosclerosis

Atherosclerosis (AS) constitutes a major threat to human health, yet most current therapeutics are hindered in achieving desirable clinical outcomes by low bioavailability or serious side effects. Herein, we constructed an enzyme-responsive and macrophage-targeting drug delivery system (SIM@HA-MSN)...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutics 2022-06, Vol.14 (6), p.1265
Main Authors: Song, Kechen, Tang, Zhuang, Song, Zhiling, Meng, Shiyu, Yang, Xiaoxue, Guo, Hui, Zhu, Yizhun, Wang, Xiaolin
Format: Article
Language:English
Subjects:
Atherosclerosis
Bioavailability
Biocompatibility
Biotechnology
Drug delivery systems
enzyme-responsive drug release
Enzymes
Ethanol
Fourier transforms
Hyaluronic acid
Inflammation
Lipids
Lipoproteins
mesoporous silica nanoparticles
Nanoparticles
simvastatin
Tumor necrosis factor-TNF
Ultrasonic imaging
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Atherosclerosis (AS) constitutes a major threat to human health, yet most current therapeutics are hindered in achieving desirable clinical outcomes by low bioavailability or serious side effects. Herein, we constructed an enzyme-responsive and macrophage-targeting drug delivery system (SIM@HA-MSN) which can potentially modulate the microenvironment of the atherosclerotic plaques characterized by excessive inflammation and overexpression of hyaluronidase (HAase) for precise AS treatment. More specifically, mesoporous silica nanoparticles (MSNs) were loaded with a lipid-lowering drug simvastatin (SIM) and further gated with hyaluronic acid (HA) coating, which endowed the nanosystem with HAase responsiveness and targetability to inflammatory macrophages. Our results showed that a high loading efficiency (>20%) and excellent enzyme-responsive release of SIM were simultaneously achieved for the first time by silica-based nanocarriers through formulation optimizations. Moreover, in vitro experiments confirmed that SIM@HA-MSN possessed robust targeting, anti-inflammatory, and anti-foaming effects, along with low cytotoxicity and excellent hemocompatibility. In addition, preliminary animal experiments demonstrated the as-established nanosystem had a long plasma-retention time and good biocompatibility in vivo. Taken together, SIM@HA-MSN with HA playing triple roles including gatekeeping, lesion-targeting, and long-circulating holds great potential for the management of atherosclerosis.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14061265