DataVXAdvanced MaterialsPaper
journal article·2024-03Open access

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

Thomas Gréa, Guillaume Jacquot, Arthur Durand, Clélia Mathieu, Adeline Gasser, Chen Zhu, Mainak Banerjee, Elyse Hucteau, Joris Mallard, Pedro Lopez Navarro, Bogdan V. Popescu, Eloise Thomas, David Kryza, Jacqueline Sidi‐Boumedine, Giuseppe Ferrauto, Eliana Gianolio, Guillaume Fleith, Jérôme Combet, Susana Brun, Stéphane Erb, Sarah Cianferani, Loïc J. Charbonnière, Lyne Fellmann, Céline Mirjolet, Laurent David, Olivier Tillement, François Lux, Sébastien Harlepp, Xavier Pivot, Alexandre Detappe

Advanced Materials· Volume 36· Issue 13
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Source abstract

Abstract

Abstract 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.
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Research context

PolymersBiomaterials

OpenAlex topics: Advanced Drug Delivery Systems · Monoclonal and Polyclonal Antibodies Research · Platelet Disorders and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institut Lumière Matière UMR 5306 Université Claude Bernard Lyon1‐CNRS University of Lyon Villeurbanne Cedex 69622 France

Université Claude Bernard Lyon 1 INSA Lyon Jean Monnet University CNRS, UMR 5223 Ingénierie des Matériaux Polymères (IMP) Villeurbanne Cedex 69622 France

Institute of Cancerology Strasbourg Europe (ICANS) Strasbourg 67000 France

Nano‐H St Quentin Fallavier 38070 France

Strasbourg Drug Discovery and Development Institute (IMS) Strasbourg 67000 France

MexBrain 13 avenue Albert Einstein Villeurbanne 69100 France

Equipe de Synthèse Pour l'Analyse Institut Pluridisciplinaire Hubert Curien (IPHC) UMR 7178 CNRS/University of Strasbourg Strasbourg Cedex 2 67087 France

Biomedicine Research Centre of Strasbourg (CRBS) Mitochondria, oxidative stress and muscular protection laboratory (UR 3072) Strasbourg 67000 France

LAGEPP University Claude Bernard Lyon 1 CNRS UMR 5007 Villeurbanne Cedex 69622 France

Imthernat Plateform Hospices Civils of Lyon Lyon 69002 France

Molecular Imaging Center Department of Molecular Biotechnology and Health Sciences University of Turin Turin 10124 Italy

Université de Strasbourg CNRS, Institut Charles Sadron (UPR 22) 23 rue du Loess, 67034 Strasbourg Cedex 2 BP 84047 France

Poly‐Dtech Strasbourg 67100 France

Laboratoire de Spectrométrie de Masse BioOrganique IPHC UMR 7178 University of Strasbourg CNRS Strasbourg 67087 France

Infrastructure Nationale de Protéomique ProFI – FR2048 Strasbourg 67087 France

SILABE Université of Strasbourg fort Foch Niederhausbergen 67207 France

Radiation Oncology Department Preclinical Radiation Therapy and Radiobiology Unit Centre Georges‐François Leclerc Unicancer Dijon 21000 France

TIReCS team INSERM UMR 1231 Dijon 21000 France

University Institute of France (IUF) Paris 75231 France

Funding

H2020 European Research Council · Agence Nationale de la Recherche

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