Mesoporous silica nanoparticles as a delivery system for improving antiangiogenic therapy

Abstract

Jian-Guo Sun,1–3,* Qin Jiang,4,* Xiao-Pei Zhang,4,* Kun Shan,1 Bai-Hui Liu,5 Chen Zhao,1 Biao Yan1,2 1Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; 2NHC Key Laboratory of Myopia, Fudan University, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China; 3Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China; 4The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; 5Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai, China *These authors contributed equally to this work Purpose: Antiangiogenic drugs usually have short-acting efficacy and poor treatment compliance. The purpose of this study was to determine whether mesoporous silica nanoparticles (MSNs) could be utilized as a nanodrug delivery system for improving antiangiogenic therapy. Materials and methods: MSN-encapsulated bevacizumab nanoparticles were prepared by the nanocasting strategy and characterized by Fourier transform infrared, transmission electron microscopy, and Brunauer–Emmett–Teller method. Encapsulation efficiency and drug loading efficiency of MSN-encapsulated bevacizumab nanoparticles were calculated. The pharmacokinetics, cytotoxicity, and tissue toxicity were evaluated in vitro and in vivo. The antiangiogenic effects of MSN-bevacizumab nanoparticles were evaluated in vitro and in vivo. Results: MSN encapsulation could prolong the residency of bevacizumab in vitreous/aqueous humor and maintain the long-lasting drug concentration. MSN-encapsulated bevacizumab nanoparticles did not show any obvious cytotoxicity and tissue toxicity. MSN-encapsulated bevacizumab nanoparticles were more effective than bevacizumab in suppressing vascular endothelial growth factor-induced endothelial cell proliferation, migration, and tube formation in vitro. MSN-encapsulated bevacizumab nanoparticles showed sustained inhibitory effects on corneal neovascularization and retinal neovascularization in vivo. Conclusion: This study provides a novel strategy of encapsulating bevacizumab to protect and deliver it, which could increase the time between administration and formulation shelf-life. MSN-encapsulated bevacizumab is a promising drug delivery alternative of antiangiogenic therapy. Keywords: mesoporous silica nanoparticle, bevacizumab, ocular angiogenesis, antiangiogenic therapy

Keywords

• mesoporous silica nanoparticle
• bevacizumab
• ocular angiogenesis
• anti-angiogenic therapy