Development and characterization of sorafenib-loaded lipid nanocapsules for the treatment of glioblastoma

Autor: Clément Tétaud, Emilie Roger, Laurent Lemaire, Philippe Menei, Anne Clavreul, Milad Pourbaghi-Masouleh
Přispěvatelé: Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Division of Drug Delivery and Tissue Engineering [Nottingham, UK], University of Nottingham, UK (UON)-School of Pharmacy [Nottingham, UK], Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales [SFR ICAT - UA] (PRISM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), This research was supported by grants from the ‘Fondation de France,’‘Ligue contre le Cancer du Grand-Ouest, Comite Departemental duMaine-et-Loire,’ ‘Association en Avant la Vie,’ and the EuropeanCommission, Education, Audiovisual and Culture Executive Agency(EACEA), through the NanoFar Erasmus Mundus joint Doctoral program., Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), School of Pharmacy [Nottingham, UK]-University of Nottingham, UK (UON), Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales (PRISM [SFR ICAT - UA])
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Drug Delivery
Drug Delivery, 2018, 25 (1), pp.1756-1765. ⟨10.1080/10717544.2018.1507061⟩
Drug Delivery, Taylor & Francis, 2018, 25 (1), pp.1756-1765. ⟨10.1080/10717544.2018.1507061⟩
Drug Delivery, Vol 25, Iss 1, Pp 1756-1765 (2018)
ISSN: 1521-0464
1071-7544
DOI: 10.1080/10717544.2018.1507061⟩
Popis: International audience; Anticancer agents that target both tumor cells and angiogenesis are of potential interest for glioblastoma (GB) therapy. One such agent is sorafenib (SFN), a tyrosine kinase inhibitor. However, poor aqueous solubility and undesirable side effects limit its clinical application, including local treatment. We encapsulated SFN in lipid nanocapsules (LNCs) to overcome these drawbacks. LNCs are nanocarriers formulated according to a solvent-free process, using only components that have received regulatory approval. SFN-LNCs had a diameter of 54 ± 1 nm, high encapsulation efficiency (>90%), and a drugpayload of 2.11 ± 0.03mg/g of LNC dispersion. They inhibited in vitro angiogenesis and decreased human U87MG GB cell viability similarly to free SFN. In vivo studies showed that the intratumoral administration of SFN-LNCs or free SFN in nude mice bearing an orthotopic U87MG human GB xenograft decreased the proportion of proliferating cells in the tumor relative to control groups. SFN-LNCs were more effective than free SFN for inducing early tumor vascular normalization, characterized by increases in tumor blood flow and decreases in tumor vessel area. These results highlight the potentialof LNCs as delivery systems for SFN. The vascular normalization induced by SFN-LNCs could be used to improve the efficacy of chemotherapy or radiotherapy for treating GB.
Databáze: OpenAIRE
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