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Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles
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Long-acting injectable nanoparticle formulation for sustained release of anti-TNF-α antibody therapeutic in

Yicheng Zhang1, Ling Li2, Jiayuan Kong1

  • 1Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|February 20, 2025
PubMed

Inflammatory bowel diseases (IBD) are chronic, remitting, and relapsing conditions of the gastrointestinal tract with incompletely elucidated etiology. The anti-TNF-α mAbs represent one of aflash nanocomplexation and flash nanoprecipitation process, resulting in particles with a narrow size distribution and tunable release profile, with the longest in vitro release lasting over four months. These mAb-releasing NPs are then incorporated into hyaluronic acid hydrogel microparticles (MPs) to enhance tissue retention, thus extending the duration of mAb release in vivo. A single i.m. injection of the LAI can maintain the serum mAb level above the therapeutically effective concentration for over 100 days in healthy mice. In a 9-week study using a dextran sulfate-induced chronic colitis model, the anti-TNF-α LAI formulation demonstrates substantial therapeutic efficacy and a better safety profile than free mAb injections. This work demonstrates the effectiveness of this LAI system in maintaining a persistent serum mAb level and its potential as a versatile, safer, and effective delivery system for antibody therapeutics.

Keywords:
Chronic colitisFlash nanocomplexationFlash nanoprecipitationHyaluronic acid hydrogelInflammatory bowel diseaseLong-acting injectableSustained releaseTNF-α antibody

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