Mesoporous silica nanoparticles as a delivery system for improving antiangiogenic therapy

Abstract

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

Acknowledgments

This work was generously supported by the grants from the National Natural Science Foundation of China (Grant No.81770945 to B.Y., and Grant No. 81570859 to Q.J.), and the grant from the Shanghai Youth Talent Support Program (to B.Y.).

Disclosure

The authors report no conflicts of interest in this work.