a 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.
b State Key Laboratory of Long-Acting and Targeting Drug Delivery System , Shandong Luye Pharmaceutical Co., Ltd. , Yantai , Shandong Province , People's Republic of China.
Drug Deliv. 2018 Nov;25(1):1372-1383. doi: 10.1080/10717544.2018.1474967.
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.
贝伐单抗是一种抗血管内皮生长因子药物，可用于治疗脉络膜新生血管（CNV）。贝伐单抗负载多泡脂质体（Bev-MVLs）已被设计和开发用于增加贝伐单抗的玻璃体内保留时间并减少注射次数。在这项研究中，通过双乳化技术制备了具有高包封效率的 Bev-MVLs，并测定了抗体活性。结果表明，10%的人血清白蛋白（HSA）可以保持贝伐单抗的活性。Bev-MVLs 的体外释放似乎呈更持续的方式，Bev-MVLs 的潜在机制表明，贝伐单抗通过扩散和侵蚀从 MVLs 中释放。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）的结果表明，贝伐单抗在体外从 MVLs 释放后可以保持其结构完整性。体内成像用于评估抗体在大鼠眼中的保留时间，而药代动力学分析则在兔眼中进行。这些结果表明，与贝伐单抗溶液（Bev-S）相比，Bev-MVLs 表现出持续释放的效果。与 Bev-S 相比，Bev-MVLs 在治疗后 28 天可以有效抑制 CNV 病变的厚度。此外，这些数据表明，Bev-MVLs 在增加玻璃体内贝伐单抗保留时间方面具有生物学可行性。因此，这种新型 Bev-MVLs 可能成为治疗 CNV 的有前途的缓释药物递送系统。
