ZIF-8 nanoparticles coated with macrophage-derived microvesicles for sustained, targeted delivery of dexamethasone to arthritic joints

Abstract

Dexamethasone sodium phosphate (Dex) is widely used in the clinic for the treatment of rheumatoid arthritis. However, it circulates in the blood for a short time and it is linked to a high risk of severe side effects caused by repeated dosing. Here, we encapsulated Dex onto zeolitic imidazolate framework-8 (ZIF-8) to prepare metal–organic framework nanoparticles with high drug loading efficiency. To prevent clearance by the mononuclear phagocyte system and extend time in circulation, the nanoparticles were also camouflaged with macrophage-derived microvesicles (MV) to obtain the biomimetic drug delivery system MV/Dex/ZIF-8. In vitro and in vivo experiments showed that the nanosystem had high drug loading and encapsulation efficiency, high stability, and long circulation time, and it permitted sustained drug release longer in inflamed joint tissues. Our study provides new insights into designing camouflaged drug carriers to prevent their phagocytosis and prolong their time in circulation.

Keywords:

• Rheumatoid arthritis
• dexamethasone sodium phosphate
• zeolitic imidazolate framework-8
• microvesicle
• extended blood circulation time

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81803478, 2018), the Key Project of Application and Basic Research of Southwest Medical University (2021ZKZD016, 2021), and the Special Support Project for Young Talents of Southwest Medical University (2020–2022).