ABSTRACT
Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.
ABSTRACT
Objective To study the clinical effect of leflunomide combined with methotrexate in the treatment of skin lesions caused by psoriatic arthritis .Methods The clinical data of 90 patients with skin lesions caused by psoriatic arthritis were collected ,and they were divided into control group and observation group by simple random method,45 cases in each group.The control group was treated with methotrexate ,and the observation group was given leflunomide combined with methotrexate .Before treatment and after treatment for one month ,two months ,three months ,the skin lesions , psoriatic arthritis symptoms improvement , clinical effects and adverse reactions were observed in the two groups.Results After treatment for one month,two months,three months,the DLQL index scores in the observation group were (8.12 ±2.02)points,(6.55 ±1.47)points,(3.68 ±1.21)points,respectively,which were significantly better than those in the control group (t=2.54,3.92,4.44,P=0.01,0.01,0.01).After treatment for one month,two months,three months,the PASI index scores in the observation group were (7.57 ±3.22)points, (4.61 ±1.86)points,(3.11 ±2.17)points,respectively,which were better than those in the control group (t=3.42, 7.81,4.07,P =0.01,0.01,0.01).The total effective rate of the observation group was 88.89％,which was significantly higher than 68.89％of the control group (χ2 =5.40,P=0.02).No serious adverse reactions occurred in both two groups,and the difference was not statistically significant (11.11％ vs.13.33％,χ2 =0.10,P=0.75). Conclusion Compared with methotrexate alone , leflunomide combined with methotrexate in the treatment of skin lesions caused by psoriatic arthritis has obvious effect , and can significantly improve the symptoms of patients with skin and arthritis symptoms ,and it is more conducive to relieve patients'pain.