Adalimumab Decorated Nanoparticles Enhance Antibody Stability and Therapeutic Outcome in Epithelial Colitis Targeting

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with increasing incidence worldwide. Although a deeper understanding of the underlying mechanisms of IBD has led to new therapeutic approaches, treatment options are still limited. Severe adverse events in conventional drug therapy and poor drug targeting are the main cause of early therapy failure. Nanoparticle-based targeting approaches can selectively deliver drugs to the site of inflammation and reduce the risk of side effects by decreasing systemic availability. Here, we developed a nanoparticulate platform for the delivery of the anti-TNF-α antibody adalimumab (ADA) by covalent crosslinking to the particle surface. ADA binding to nanoparticles improved the stability of ADA against proteolytic degradation in vitro and led to a significantly better therapeutic outcome in a murine colitis model. Moreover, immobilization of ADA reduced systemic exposure, which can lead to enhanced therapeutic safety. Thus, nanoparticle protein decoration constitutes a platform through which epithelial delivery of any biological of interest to the inflamed gut and hence a local treatment can be achieved.

Active nanoparticle targeting of MUC5AC ameliorates therapeutic outcome in experimental colitis

“…In the inflammation state, the activity of proteases is strongly upregulated contributing to the pathogenesis of colitis, 48 which can lead to an inactivation of the antibody. However, Ries et al 49 showed that covalent immobilization of antibodies on NPs strongly enhanced their stability against proteolytic degradation. This is also in line with the results of this study, sufficiently high binding ability of anti-MUC5 was maintained.…”

Development of nanoparticle‐based drug delivery system for inflammation treatment and diagnosis

“…To construct LFA‐1 modified SPIO nanoparticles, first, oleic acid capped SPIO nanocrystals were encapsulated with a layer of phospholipid consisting of 80% n‐poly(ethylene glycol) phosphatidylethanolamine (DPPE‐PEG) and 20% dioleoyl‐glycero‐succinyl‐nitrilotriacetic acid (DOGS‐NTA). Then, the LFA‐1 I domain with His tag was conjugated with nickel ions robustly chelated by amide bonds via high affinity to attain the targeted SPIO nanoparticles 69,107–110 …”

“…Then, the LFA-1 I domain with His tag was conjugated with nickel ions robustly chelated by amide bonds via high affinity to attain the targeted SPIO nanoparticles. 69,[107][108][109][110]…”