Since the approval of recombinant human insulin in 1982, there has been a growing interest in the use of biotherapeutics, and more particularly of monoclonal antibodies (mAb)-based products due to their multiple advantages compared to small chemical entities. Nonetheless, mAbs also show some drawbacks, one of them being their sensitivity to diverse instability pathways due to their complex structure. Therefore, attention needs to be paid during formulation and storage of such entities. While administration of mAbs using non-invasive routes has been extensively investigated, it still faces several challenges, especially regarding systemic therapy. Thus, parenteral route currently remains the main route of administration for antibodies (Abs). However, frequent injections are required in order to maintain Ab plasma levels into the therapeutic range, which may induce peak-to-trough fluctuations in blood levels due to multiple dosing as well as poor patient compliance. Consequently, methods to increase the half-life of Abs have gained interest over the last decades, and more particularly the use of sustained-delivery systems based on poly(lactide-co-glycolide) acid (PLGA) derivatives. In this work, the spray-drying of a water-in-oil emulsion (w/o) was selected as the formulation technique to produce Ab-loaded PLGA microparticles. Based on the requirement of sustained-release delivery systems, different objectives were set regarding the characteristics of the microparticles, i.e. a drug loading (DL) of at least 20%, a continuous in vitro and in vivo Ab release over a minimum of one month with a limited burst release and the possibility to maintain Ab stability during manufacturing, storage and release. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished
| Identifer | oai:union.ndltd.org:ulb.ac.be/oai:dipot.ulb.ac.be:2013/332586 |
| Date | 12 October 2021 |
| Creators | Arrighi, Audrey |
| Contributors | Amighi, Karim, Goole, Jonathan, Langer, Ingrid, Van Antwerpen, Pierre, Delporte, Cédric, De Braekeleer, Kris, Benali, Samira, Vanbever, Rita |
| Publisher | Universite Libre de Bruxelles, Université libre de Bruxelles, Faculté de Pharmacie, Bruxelles |
| Source Sets | Université libre de Bruxelles |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:ulb-repo/semantics/doctoralThesis, info:ulb-repo/semantics/openurl/vlink-dissertation |
| Format | 3 full-text file(s): application/vnd.openxmlformats-officedocument.wordprocessingml.document | application/pdf | application/pdf |
| Rights | 3 full-text file(s): info:eu-repo/semantics/openAccess | info:eu-repo/semantics/closedAccess | info:eu-repo/semantics/restrictedAccess |
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