Combined Anti-Angiogenic and Anti-Inflammatory Nanoformulation for Effective Treatment of Ocular Vascular Diseases

Abstract

Jianguo Sun,1,* Huiling Nie,2,* Panpan Pan,3,* Qin Jiang,2,* Chang Liu,1 Min Wang,1 Yonghui Deng,3,4 Biao Yan1 1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People’s Republic of China; 2The Affiliated Eye Hospital and The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Chemistry, Fudan University, Shanghai, People’s Republic of China; 4Department of Gastroenterology and Hepatology, Zhongshan Hospital, Institute of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghui Deng; Biao Yan, Email [email protected]; [email protected]: Ocular vascular diseases are the major causes of visual impairment, which are characterized by retinal vascular dysfunction and robust inflammatory responses. Traditional anti-angiogenic or anti-inflammatory drugs still have limitations due to the short-acting effects. To improve the anti-angiogenic or anti-inflammatory efficiency, a dual-drug nanocomposite formulation was proposed for combined anti-angiogenic and anti-inflammatory treatment of ocular vascular diseases.Methods: : CBC-MCC@hMSN(SM) complex nanoformulation was prepared by integrating conbercept (CBC, an anti-angiogenic drug) and MCC950 (MCC, an inhibitor of inflammation) into the surface-modified hollow mesoporous silica nanoparticles (hMSN(SM)). CBC-MCC@hMSN(SM) complex nanoformulation was then characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, zeta potentials, and nitrogen adsorption-desorption measurement. CBC and MCC release profile, cytotoxicity, tissue toxicity, anti-angiogenic effects, and anti-inflammatory effects of CBC-MCC@hMSN(SM) were estimated using the in vitro and in vivo experiments.Results: CBC-MCC@hMSN(SM) complex had no obvious cytotoxicity and tissue toxicity and did not cause a detectable ocular inflammatory responses. CBC-MCC@hMSN(SM) complex was more effective than free CBC or MCC in suppressing endothelial angiogenic effects and inflammatory responses in vitro. A single intraocular injection of CBC-MCC@hMSN(SM) complex potently suppressed diabetes-induced retinal vascular dysfunction, choroidal neovascularization, and inflammatory responses for up to 6 months.Conclusion: : Combined CBC and MCC nanoformulation provides a promising strategy for sustained suppression of pathological angiogenesis and inflammatory responses to improve the treatment outcomes of ocular vascular diseases.Keywords: combined nanocomposite formulation, mesoporous silica nanoparticle, anti-angiogenesis, anti-inflammation, ocular vascular disease

Keywords

• dual-drug nanocomposite formulation
• mesoporous silica nanoparticle
• anti-angiogensis
• anti-inflammation
• ocular vascular disease