Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy

载有小细胞外囊泡的贝伐单抗可减少糖尿病视网膜病变所需的玻璃体内注射频率

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作者:Shivakumar K Reddy, Abhijna R Ballal, S Shailaja, Raviraja N Seetharam, Chandrashekar H Raghu, Runali Sankhe, Kanthilatha Pai, Tenzin Tender, Mary Mathew, Annayya Aroor, Ashok K Shetty, Shalini Adiga, Vasudha Devi, Manjunatha S Muttigi, Dinesh Upadhya

Conclusion

This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.

Methods

As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR.

Results

The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab.

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