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Intra-articular delivery of full-length antibodies through the use of an in situ forming depot
- Source :
- Journal of Controlled Release, Journal of Controlled Release, 2022, 341, pp.578-590. ⟨10.1016/j.jconrel.2021.12.010⟩
- Publication Year :
- 2022
- Publisher :
- HAL CCSD, 2022.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 01683659
- Database :
- OpenAIRE
- Journal :
- Journal of Controlled Release, Journal of Controlled Release, 2022, 341, pp.578-590. ⟨10.1016/j.jconrel.2021.12.010⟩
- Accession number :
- edsair.doi.dedup.....411cc2189489471e6474a3a8b018af48