Multivesicular liposomes for sustained release of bevacizumab in treating laser-induced choroidal neovascularization

Drug Delivery

Hongjie Mu¹  Ying Jiang¹  Aiping Wang¹  Yongchao Chu¹  Liuxiang Chu¹  Kaoxiang Sun¹  Yiyun Wang¹  Hongchen Hua¹  Kaili Wang¹  Wanhui Liu²  Fenghua Fu²  Youxin Li² 

[1] School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong Province, People’s Republic of China;School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong Province, People’s Republic of China;State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd., Yantai, Shandong Province, People’s Republic of Chin;

关键词: Bevacizumab;    choroidal neovascularization;    multivesicular liposomes;    bioactivity;    intravitreal injection;    vitreous humor;   

DOI  :  10.1080/10717544.2018.1474967

来源: publisher

【 摘 要 】

Bevacizumab is an anti-vascular endothelial growth factor drug that can be used to treat choroidal neovascularization (CNV). Bevacizumab-loaded multivesicular liposomes (Bev-MVLs) have been designed and developed to increase the intravitreal retention time of bevacizumab and reduce the number of injection times. In this study, Bev-MVLs with high encapsulation efficiency were prepared by double emulsification technique, and antibody activity was determined. The results revealed that 10% of human serum albumin (HSA) could preserve the activity of bevacizumab. In vitro release of Bev-MVLs appeared to be in a more sustained manner, the underlying mechanisms of Bev-MVLs indicated that bevacizumab was released from MVLs through diffusion and erosion. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that bevacizumab could retain its structural integrity after being released from MVLs in vitro. In vivo imaging was used to evaluate the retention time of antibody in rat eyes, while pharmacokinetic analysis was performed on rabbit eyes. These results indicated that Bev-MVLs exhibited sustained release effects as compared to bevacizumab solution (Bev-S). Bev-MVLs could effectively inhibit the thickness of CNV lesion as compared to Bev-S at 28 days after treatment. Furthermore, these data suggest that Bev-MVLs are biologically feasible to increase the retention time of bevacizumab in vitreous humor. This novel Bev-MVLs may therefore serve as a promising sustained release drug delivery system for the treatment of CNV.

【 授权许可】

CC BY