Related Experiment Video
Updated: Nov 20, 2025
Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
PLGA/PCADK composite microspheres containing hyaluronic acid-chitosan siRNA nanoparticles: A rational design for
Menghui Zhao1, Tianyu Zhu1, Jicong Chen1
1School of Life Sciences, Jilin University, Changchun, Jilin, China.
Abstract:
Myeloid cell leukemia-1 (Mcl-1), a member of the Bcl-2 anti-apoptotic family, is overexpressed in the synovial macrophages of patients with rheumatoid arthritis (RA). Small interfering RNA (siRNA) Mcl-1 can induce macrophage apoptosis in the joints and is a potential therapeutic target of RA. Nevertheless, the application of siRNA is limited owing to its instability and susceptibility to degradation in vivo. To address these shortcomings, we developed composite microspheres (MPs) loaded with hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs). First, we synthesized HA-CS/siRNA NPs (HCNPs) using ionotropic gelation process. Then, HCNPs, as an internal aqueous phase, were loaded into poly (D, L-lactide-co-glycolide) (PLGA) and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) MPs using the double emulsion method. The NPs-in-MPs (NiMPs) composite system provided sustained release of NPs, protected siRNA against nuclease degradation in the serum, and could readily cross the cellular membrane. In addition, we evaluated the advantages of NiMPs in an adjuvant-induced arthritis rat model. Our experimental results demonstrate that NiMPs have greater pharmacodynamic effects than common MPs. Meanwhile, compared with HCNPs, NiMPs reduced the frequency of drug administration. Therefore, NiMPs are a promising and novel siRNA delivery vehicle for RA therapy.
Insights
New composite microspheres effectively deliver siRNA to treat rheumatoid arthritis (RA). This novel nanoparticle-in-microsphere system protects the therapeutic agent and improves treatment efficacy, reducing administration frequency.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Rheumatology
Background:
- Myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein, is overexpressed in rheumatoid arthritis (RA) synovial macrophages.
- Small interfering RNA (siRNA) targeting Mcl-1 can induce apoptosis in joint macrophages, presenting a potential RA therapeutic strategy.
- Current siRNA delivery faces limitations due to instability and degradation in vivo.
Purpose of the Study:
- To develop a novel composite system for enhanced siRNA delivery for rheumatoid arthritis (RA) therapy.
- To create hyaluronic acid-chitosan nanoparticles (HCNPs) loaded with siRNA.
- To encapsulate HCNPs within poly (D, L-lactide-co-glycolide) and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) microspheres (MPs) to form NPs-in-MPs (NiMPs).
Main Methods:
- Synthesized HA-CS/siRNA NPs (HCNPs) via ionotropic gelation.
- Fabricated NiMPs using a double emulsion method, encapsulating HCNPs within PLGA/PCADK MPs.
- Evaluated NiMPs in an adjuvant-induced arthritis rat model, assessing pharmacodynamics and administration frequency.
Main Results:
- The NiMPs system demonstrated sustained release of NPs and protected siRNA from nuclease degradation.
- NiMPs effectively crossed cellular membranes.
- In the adjuvant-induced arthritis rat model, NiMPs exhibited superior pharmacodynamic effects and required less frequent administration compared to conventional MPs and HCNPs.
Conclusions:
- The developed NiMPs composite system offers a promising solution for overcoming the limitations of siRNA delivery in RA.
- NiMPs provide enhanced therapeutic efficacy and improved dosing convenience for rheumatoid arthritis treatment.
- This novel siRNA delivery vehicle holds significant potential for advancing RA therapy.
More Related Videos
05:55Synthesis and Characterization of Placental Chondroitin Sulfate A plCSA-Targeting Lipid-Polymer Nanoparticles
Published on: September 18, 2018
09:36Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo
Published on: February 5, 2019