PLGA/PCADK composite microspheres containing hyaluronic acid–chitosan siRNA nanoparticles: A rational design for rheumatoid arthritis therapy
| Autor: | Lesheng Teng, Yaxin Cui, Xueyan Zhang, Youxin Li, Tianyu Zhu, Jicong Chen, Fengying Sun, Menghui Zhao, Robert J. Lee |
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| Rok vydání: | 2021 |
| Předmět: |
Small interfering RNA
Cell Pharmaceutical Science Arthritis 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Arthritis Rheumatoid Chitosan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Hyaluronic acid medicine Animals Humans Hyaluronic Acid RNA Small Interfering Rational design 021001 nanoscience & nanotechnology medicine.disease Microspheres Rats PLGA medicine.anatomical_structure chemistry Nanoparticles 0210 nano-technology |
| Zdroj: | International Journal of Pharmaceutics. 596:120204 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2021.120204 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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