Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies.

Fiche publication

Date publication

décembre 2023

Journal

Advanced materials (Deerfield Beach, Fla.)

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CHARBONNIERE Loïc , Dr CIANFERANI Sarah , Dr MIRJOLET Céline , Pr PIVOT Xavier , Dr HARLEPP Sébastien , Dr DETAPPE Alexandre , Dr HUCTEAU Elyse , Dr MALLARD Joris

Tous les auteurs :
Gréa T, Jacquot G, Durand A, Mathieu C, Gasser A, Zhu C, Banerjee M, Hucteau E, Mallard J, Lopez Navarro P, Popescu BV, Thomas E, Kryza D, Sidi-Boumedine J, Ferrauto G, Gianolio E, Fleith G, Combet J, Brun S, Erb S, Cianferani S, Charbonnière LJ, Fellmann L, Mirjolet C, David L, Tillement O, Lux F, Harlepp S, Pivot X, Detappe A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/38105299

Résumé

Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA-/EMA-approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tissue permeability. However, this method lacks tunable release properties, requiring individual optimization for each mAb. Seeking alternatives, physical polysaccharide hydrogels emerge as promising candidates due to their tunable physicochemical and biodegradability features. Unfortunately, none have demonstrated simultaneous biocompatibility, biodegradability, and controlled release properties for large proteins (≥150 kDa) after SC delivery in clinical settings. Here, a novel two-component hydrogel comprising chitosan and chitosan@DOTAGA is introduced that can be seamlessly mixed with sterile mAbs formulations initially designed for intravenous (IV) administration, repurposing them as novel tunable SC formulations. Validated in mice and nonhuman primates (NHPs) with various mAbs, including trastuzumab and rituximab, the hydrogel exhibited biodegradability and biocompatibility features. Pharmacokinetic studies in both species demonstrated tunable controlled release, surpassing the capabilities of rHuPH20, with comparable parameters to the rHuPH20+mAbs formulation. These findings signify the potential for rapid translation to human applications, opening avenues for the clinical development of this novel SC biosimilar formulation.