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

Markus Ries,Brice Moulari,Maryam A. Shetab Boushehri,Daniel Molnar,Yann Pellequer,Mohamed Ehab Ali,Arnaud Béduneau,Alf Lamprecht

doi:10.3390/pharmaceutics14020352

Markus Ries, Brice Moulari + Show 6 more

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https://doi.org/10.3390/pharmaceutics14020352

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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.

Highlights

IntroductionInflammatory bowel disease (IBD), in its two main forms i.e., ulcerative colitis (UC)
Inflammatory bowel disease (IBD), in its two main forms i.e., ulcerative colitis (UC)and Crohn’s disease (CD), is a progressive, relapsing-remitting disorder of the gastrointestinal tract, characterized by epithelial and submucosal damage and intestinal inflammation [1]
A significant increase of 18 nm in Z-Average for ADA-NP and of 2 nm for Bovine serum albumin (BSA)-NP was found relative to the blank nanoparticles (BL-NP)

Summary

Introduction

Inflammatory bowel disease (IBD), in its two main forms i.e., ulcerative colitis (UC). Crohn’s disease (CD), is a progressive, relapsing-remitting disorder of the gastrointestinal tract, characterized by epithelial and submucosal damage and intestinal inflammation [1]. Cytokines play a crucial role in the pathogenesis of UC, driving intestinal inflammation and the associated clinical symptoms [4,5]. Tumor necrosis factor (TNF)-α has been identified as a key cytokine in the treatment regimen of moderate to severe UC [6]. Conventional pharmacotherapy consists of anti-inflammatory and immunosuppressive treatment, e.g., 5-aminosalicylic acid, budesonide or azathioprine, with the goal of inducing and maintaining remission of inflammation or colonic mucosal healing [7,8]. The development of biologicals, including the antibody adalimumab (ADA), which binds to TNFα and neutralizes its biological function, has greatly improved treatment options in UC

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