Background: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration, serious adverse reactions during long-term administration. To achieve better treatment, reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results: The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo biodistribution experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility. Conclusion: The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

BackgroundPrednisolone (PD) is extremely effective for treating rheumatoid arthritis (RA). However, it distributes nonspecifically throughout the body and its use is associated with serious side effects, which promoted us to compound it into a phytomedicine for greater efficacy and safety.MethodsWe combined PD with curcumin (CU), an effective monomer from traditional Chinese medicine, and human serum albumin (HSA) in a nanoparticulate system (N-PD/CU) to compensate for the poor bioavailability of PD and CU. N-PD/CU was prepared by high-pressure homogenization, and its characteristics were evaluated in vitro. Next, we investigated its toxicity and mechanism of anti-inflammatory to macrophages. Finally, its pharmacokinetics, biodistribution and therapeutic efficacy were assessed in rats with adjuvant-induced arthritis (AIA).ResultsN-PD/CU showed a narrow size distribution around 150.4 ± 2.4 nm, a polydispersity index of 0.22 ± 0.02 and drug loading efficiency (DLE) of 88.75 ± 1.82% for PD and 85.79 ± 1.43% for CU. N-PD/CU showed sustained release of both drugs in vitro. N-PD/CU had no toxicity to macrophages in vitro on concentrations between 0.1 and 1.2 μmol/mL. In activated macrophages, N-PD decreased levels of pro-inflammatory cytokines, while N-CU increased levels of anti-inflammatory IL-10, and N-PD/CU exhibited best therapeutic effect in vitro, suggesting co-delivery of PD and CU may synergistically control the course of RA. In AIA rats, N-PD/CU accumulated in inflamed joints through the effect of extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS effect) in inflammatory lesion and showed higher therapeutic efficacy than single-loaded nanoparticles, either free drug on its own, or a simple mixture of the two drugs.ConclusionThis codelivery system based on HSA is a promising platform for combination chemotherapy in RA.

Backgroud: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo pharmacodynamic experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility. Conclusion The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

Background: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results: The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was -22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo biodistribution experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility.Conclusion: The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.