Intra-articular delivery of full-length antibodies through the use of an in situ forming depot
| Autor: | Alexis Fayd'herbe De Maudave, Wilhem Leconet, Karine Toupet, Michael Constantinides, Guillaume Bossis, Marion de Toledo, Jérôme Vialaret, Christophe Hirtz, Adolfo Lopez-Noriega, Christian Jorgensen, Daniele Noël, Pascale Louis-Plence, Sylvestre Grizot, Martin Villalba |
|---|---|
| Přispěvatelé: | Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), MedinCell SA, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Sainte Catherine [Avignon], KARLI, Mélanie |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
0303 health sciences
Local delivery Polymers [SDV]Life Sciences [q-bio] Pharmaceutical Science Biodegradable copolymers 3. Good health [SDV] Life Sciences [q-bio] Mice 03 medical and health sciences 0302 clinical medicine Delayed-Action Preparations 030220 oncology & carcinogenesis Daratumumab Animals Full length monoclonal antibodies Intra-articular Rituximab 030304 developmental biology |
| Zdroj: | Journal of Controlled Release Journal of Controlled Release, 2022, 341, pp.578-590. ⟨10.1016/j.jconrel.2021.12.010⟩ |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2021.12.010⟩ |
| Popis: | International audience; Monoclonal antibodies (mAbs) are large size molecules that have demonstrated high therapeutic potential for the treatment of cancer or autoimmune diseases. Despite some excellent results, their intravenous administration results in high plasma concentration. This triggers off-target effects and sometimes poor targeted tissue distribution. To circumvent this issue, we investigated a local controlled-delivery approach using an in situ forming depot technology. Two clinically relevant mAbs, rituximab (RTX) and daratumumab (DARA), were formulated using an injectable technology based on biodegradable PEG-PLA copolymers. The stability and controlled release features of the formulations were investigated. HPLC and mass spectrometry revealed the preservation of the protein structure. In vitro binding of formulated antibodies to their target antigens and to their cellular FcγRIIIa natural killer cell receptor was fully maintained. Furthermore, encapsulated RTX was as efficient as classical intravenous RTX treatment to inhibit the in vivo tumor growth of malignant human B cells in immunodeficient NSG mice. Finally, the intra-articular administration of the formulated mAbs yielded a sustained local release associated with a lower plasma concentration compared to the intra-articular delivery of non-encapsulated mAbs. Our results demonstrate that the utilization of this polymeric technology is a reliable alternative for the local delivery of fully functional clinically relevant mAbs. |
| Databáze: | OpenAIRE |
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