Long-acting silica formulations - In vitro study of inflammatory response in the eye

Abstract

Inflammation is body’s typical response to unnatural, pathogenic events occurring inside the individual. In the eye, inflammation is a critical condition which can lead to sever problems, including permanent loss of vision. Drug delivery to the eye is difficult and usually the most direct and best way to dose drug in the eye is via injection. Unfortunately, injections always carry a risk of complications. Thus, there is a need to develop long-acting medicines which can be dosed in less frequent manner to reduce this risk. In this master’s thesis study, the DelSiTech’s technology is studied with several different methods to obtain information of silica formulation’s effect on protein drugs. Greatest risk of these drugs is hypothesised to be related to increased aggregation levels of drug proteins. Aggregates and other (chemical) changes on proteins are monitored with reverse-phase-, size-exclusion chromatography and with microscope. The material and drug molecules are finally studied with an in vitro cytokine assay to find out if the correlation to inflammation might occur in vivo with this studied material. Studied three drug candidates: whole antibody, fusion protein and fab-fragment of an antibody. All of these are protein structures. Fusion protein has an FC-part of an antibody. As a conclusion, inflammation response related cytokine release is not observed with Fab-fragment tests and is low or reduced with added excipients for whole antibody and fusion protein tests.