Rapamycin-loaded Poly(lactic-co-glycolic) acid nanoparticles: Preparation, characterization, and in vitro toxicity study for potential intra-articular injection
[Display omitted] •Rapamycin seems a chondroprotective candidate in experimental rodent osteoarthritis.•Articular injection is helpful to optimize its profit and avoid systemic effects.•We thus developed Rapamycin-loaded nanoparticles by emulsion/evaporation method.•We evaluated Rapa-PGLA-NPs cytoco...
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Veröffentlicht in: | International journal of pharmaceutics 2021-11, Vol.609, p.121198-121198, Article 121198 |
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Sprache: | eng |
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•Rapamycin seems a chondroprotective candidate in experimental rodent osteoarthritis.•Articular injection is helpful to optimize its profit and avoid systemic effects.•We thus developed Rapamycin-loaded nanoparticles by emulsion/evaporation method.•We evaluated Rapa-PGLA-NPs cytocompatibility towards cartilage and synovium.•Rapamycin-loaded NPs exert a suitable profile for an i.a. administration (10 µM).
Osteoarthritis (OA) is the most common degenerative joint disease. Rapamycin is a potential candidate for OA treatment by increasing the autophagy process implicated in its physiopathology. To optimize Rapamycin profit and avoid systemic side effects, intra-articular (i.a.) administration appeared helpful. However, Rapamycin's highly hydrophobic nature and low bioavailability made it challenging to develop purpose-made drug delivery systems to overcome these limitations. We developed Rapamycin-loaded nanoparticles (NPs) using poly (lactic-co-glycolic acid) by emulsion/evaporation method. We evaluated these NPs' cytocompatibility towards cartilage (chondrocytes) and synovial membrane cells (synoviocytes) for a potential i.a. administration. The in vitro characterization of Rapamycin-loaded NPs had shown a suitable profile for an i.a. administration. In vitro biocompatibility of NPs was highlighted to 10 µM of Rapamycin for both synoviocytes and chondrocytes, but significant toxicity was observed with higher concentrations. Besides, synoviocytes are more sensitive to Rapamycin-loaded NPs than chondrocytes. Finally, we observed in vitro that an adapted formulated Rapamycin-loaded NPs could be safe at suitable i.a. injection concentrations. The toxic effect of Rapamycin encapsulated in these NPs on both articular cells was dose-dependent. After Rapamycin-loaded NPs i.a. administration, local retention, in situ safety, and systemic release should be evaluated with experimental in vivo models. |
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ISSN: | 0378-5173 1873-3476 |
DOI: | 10.1016/j.ijpharm.2021.121198 |