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A Bioactive Disintegrable Polymer Nanoparticle for Synergistic Vascular Anticalcification.
Hossein Adelnia1,2, Shehzahdi Shebbrin Moonshi1, Yuao Wu1
1Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, Queensland 4111, Australia.
ACS Nano
|August 31, 2023
Summary
Targeted nanoparticles carrying curcumin effectively inhibit vascular calcification by releasing poly(aspartic acid) and curcumin, preventing cell differentiation and reducing calcium deposition in vivo with minimal side effects.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Vascular Biology
Background:
- Vascular calcification is a significant risk factor for cardiovascular disease.
- Poly(aspartic acid) (PASP) shows potential for inhibiting vascular calcification but has administration challenges.
- Nanoparticle drug delivery systems offer a promising approach to overcome these limitations.
Purpose of the Study:
- To develop targeted polysuccinimide-based nanoparticles (PSI NPs) as a prodrug and carrier for enhanced vascular anticalcification therapy.
- To investigate the efficacy of PSI NPs loaded with curcumin (Cur) for synergistic vascular anticalcification effects.
- To evaluate the safety and therapeutic potential of Cur-loaded PSI NPs in vitro and in vivo.
Main Methods:
- Synthesis and characterization of polysuccinimide-based nanoparticles (PSI NPs) for PASP delivery.
- Encapsulation of hydrophobic curcumin (Cur) into PSI NPs with high loading efficiency.
- In vitro assessment of NP stability, drug release kinetics under physiological and acidic conditions, and effects on vascular smooth muscle cells (VSMCs) and macrophages.
- In vivo evaluation of Cur-loaded PSI NPs in a rat model of vascular calcification induced by adenine diet, including histological and serum biochemistry analyses.
Main Results:
- PSI NPs demonstrated stability in physiological conditions for 16 hours, slowly releasing therapeutic PASP and Cur over 48 hours.
- Cur-loaded PSI NPs exhibited pH-dependent drug release, with limited release in acidic conditions.
- While PSI NPs prevented calcium deposition, Cur-loaded PSI NPs also inhibited VSMC osteogenic differentiation and reduced ROS levels in macrophages.
- In vivo studies showed significant reduction in aortic calcification in rats treated with Cur-loaded PSI NPs, with no adverse effects on bone integrity or significant toxicity.
Conclusions:
- Chemically modified PSI NPs serve as effective nanocarriers for hydrophobic drugs, possessing anticalcification and anti-ROS activities.
- Cur-loaded PSI NPs provide a synergistic therapeutic effect, addressing both calcium deposition and VSMC osteogenic differentiation.
- This novel nanomedicine approach demonstrates significant potential for treating vascular calcification with an improved safety profile.
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