Microsphere for double protection of antibody drug and intravitreal injection, and preparation method thereof

Abstract

The invention provides a microsphere for double protection of antibody drug and intravitreal injection, and a preparation method thereof. Particles of a monoclonal antibody drug are prepared by adopting a method of water phase-water phase emulsification, polylactic acid-glycolic acid copolymer and polyketal are utilized as carrier materials, and a sustained release microsphere that wraps and carries the particles of a dextran-monoclonal antibody drug is prepared by employing an emulsion solvent volatilization method of water phase-oil phase-solid phase. Denaturation and aggregation of antibodies are caused by an acidic microenvironment of polylactic acid-glycolic acid in an organic phase/aqueous phase interface and a degradation process, the drug loading capacity of the microsphere is increased and a burst release phenomenon during a releasing process of the microsphere is reduced, and double protection on the monoclonal antibody drug of the microsphere is achieved; the polyketal enables the drug loading capacity of the microsphere to be increased, enables the stimulation of an acidic degradation product of the polylactic acid and glycolic acid on eye environment to be reduce, andenables side effects such as endophthalmitis to be reduced; and the microsphere can release the monoclonal antibody for not less than 28 days in the in vitro environment and for not less than 2 monthsin the eye, and so, the frequency of administration can be reduced, pain of patients and economic burden are reduced, and the compliance of patients is improved.

Description

technical field [0001] The invention relates to a microsphere injected into the vitreous with double protection against antibody drugs. The invention further provides a preparation method thereof, which belongs to the technical field of medicine. Background technique [0002] Retinal diseases have become the second leading cause of blindness after cataract in my country, among which age-related macular degeneration (AMD) is recognized as one of the most difficult eye diseases to treat, and choroidal neovascularization (CNV) is the most important cause of vision loss. reason. Among them, vascular endothelial growth factor (VEGF) and its receptor play an important role in the proliferation and repair of pathological neovascularization. Abnormal angiogenesis causes vascular leakage in ocular vascular disease. Therefore, anti-VEGF drugs become the key to the treatment of wet age-related macular degeneration. [0003] Aflibercept (Eylea®) is the world's first fully humanized fu...

AI Technical Summary

Problems solved by technology

However, due to the large molecular weight and fragile structure of the drug, the organic phase / water phase interface generated during the preparation process is likely to cause denaturation and aggregation of antibodies, resulting in a decrease in drug activity.

Moreover, the drug in the inner water phase is easy to diffuse into the outer water phase due to hydrophilicity, resulting in lower drug loading and encapsulation efficiency.

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