ABSTRACT
AIMS: Evaluate the effect of varying the droplet size of microspheres charged with thyme essential oil (TEO-MS) on their swelling (Sw), release rate (%RR) and in vitro antifungal activity against Saprolegnia sp. METHODS: TEO-MS obtained by ionic gelation were characterised through SEM microscopy and X-ray microtomography. Their Sw and RR% were evaluated at simulated fish-gastrointestinal conditions using gravimetric and spectrophotometric techniques. RESULTS: For all evaluated droplet sizes (p ≥ 0.05), TEO was heterogeneously distributed inside of the MS and TEO-MS experimented agglomeration and sphericity loss after the drying process. Under gastric conditions, the acid pH (2.9) limited the Sw (50-100%) of TEO-MS, generating a low RR% (14-18%). Contrary, the slightly alkaline intestinal pH (8.1) favoured the Sw (â¼3.2 to 3.8 times) and therefore the RR% (42-63%). CONCLUSIONS: TEO-MS (5-100 mg/mL) presented antifungal capacity onto Saprolegnia sp. after the simulated fish digestion, being the small droplet size once the most effective.
Subject(s)
Antifungal Agents/administration & dosage , Drug Delivery Systems , Microspheres , Oils, Volatile , Saprolegnia/drug effects , Thymus Plant/chemistry , Animals , Chemistry, Pharmaceutical/methods , Drug Liberation , Fishes , Gastrointestinal Diseases/drug therapy , Hydrogen-Ion Concentration , In Vitro Techniques , Microscopy, Electron, Scanning , Models, Theoretical , Particle Size , Spectrophotometry , X-Ray MicrotomographyABSTRACT
Hypoxia-inducible factor 1 α (HIF1α), a regulator of metabolic change, is required for the survival and differentiation potential of mesenchymal stem/stromal cells (MSC). Its role in MSC immunoregulatory activity, however, has not been completely elucidated. In the present study, we evaluate the role of HIF1α on MSC immunosuppressive potential. We show that HIF1α silencing in MSC decreases their inhibitory potential on Th1 and Th17 cell generation and limits their capacity to generate regulatory T cells. This reduced immunosuppressive potential of MSC is associated with a metabolic switch from glycolysis to OXPHOS and a reduced capacity to express or produce some immunosuppressive mediators including Intercellular Adhesion Molecule (ICAM), IL-6, and nitric oxide (NO). Moreover, using the Delayed-Type Hypersensitivity murine model (DTH), we confirm, in vivo, the critical role of HIF1α on MSC immunosuppressive effect. Indeed, we show that HIF1α silencing impairs MSC capacity to reduce inflammation and inhibit the generation of pro-inflammatory T cells. This study reveals the pivotal role of HIF1α on MSC immunosuppressive activity through the regulation of their metabolic status and identifies HIF1α as a novel mediator of MSC immunotherapeutic potential.
