Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone

磁性纳米乳剂用于关节内输送抗坏血酸和地塞米松

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作者:Camelia Mihaela Zară-Dănceanu, Cristina Stavilă, Anca Emanuela Minuti, Luminiţa Lăbușcă, Valentin Nastasa, Dumitru-Daniel Herea, Răzvan-Nicolae Malancus, Daniel Ghercă, Sorin-Aurelian Pasca, Horia Chiriac, Mihai Mares, Nicoleta Lupu

Abstract

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.

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