Parametric Drug Release Optimization of Anti-Inflammatory Drugs by Gold Nanoparticles for Topically Applied Ocular Therapy.

Eye drops represent 90% of all currently used ophthalmic treatments. Only 0.02% of therapeutic molecules contained in eye drops reach the eye anterior chamber despite their high concentration. The tear film efficiently protects the cornea, reducing access to the target. Thereby, the increase in the drug bioavailability and efficiency must come from the mucoadhesion optimization of the drug delivery system. The gold nanoparticles, used as a drug delivery system in this study, already showcased ultrastable and mucoadhesive properties. The goal was to study the gold nanoparticles' ability to release two specific ophthalmic drugs, flurbiprofen and ketorolac. The parameters of interest were those involving the loading conditions, the gold nanoparticles properties, and the release experimental conditions. The drug release was measured using an in vitro model based on dialysis bags coupled with UV-visible spectroscopy. Gold nanoparticles showed an ability to release different molecules, whether hydrophobic or hydrophilic, in passive or active drug release environments. Based on these preliminary results, gold nanoparticles could represent a promising drug delivery system for ketorolac and flurbiprofen when topically applied through eye drops.

Control of adipogenic commitment by a STAT3-VSTM2A axis.

White adipose tissue (WAT) is a dynamic organ that plays crucial roles in controlling metabolic homeostasis. During development and periods of energy excess, adipose progenitors are recruited and differentiate into adipocytes to promote lipid storage capability. The identity of adipose progenitors and the signals that promote their recruitment are still incompletely characterized. We have recently identified V-set and transmembrane domain-containing protein 2A (VSTM2A) as a novel protein enriched in preadipocytes that amplifies adipogenic commitment. Despite the emerging role of VSTM2A in promoting adipogenesis, the molecular mechanisms regulating Vstm2a expression in preadipocytes are still unknown. To define the molecular mechanisms controlling Vstm2a expression, we have treated preadipocytes with an array of compounds capable of modulating established regulators of adipogenesis. Here, we report that Vstm2a expression is positively regulated by PI3K/mTOR and cAMP-dependent signaling pathways and repressed by the MAPK pathway and the glucocorticoid receptor. By integrating the impact of all the molecules tested, we identified signal transducer and activator of transcription 3 (STAT3) as a novel downstream transcription factor affecting Vstm2a expression. We show that activation of STAT3 increased Vstm2a expression, whereas its inhibition repressed this process. In mice, we found that STAT3 phosphorylation is elevated in the early phases of WAT development, an effect that strongly associates with Vstm2a expression. Our findings identify STAT3 as a key transcription factor regulating Vstm2a expression in preadipocytes.NEW & NOTEWORTHY cAMP-dependent and PI3K-mTOR signaling pathways promote the expression of Vstm2a. STAT3 is a key transcription factor that controls Vstm2a expression in preadipocytes. STAT3 is activated in the early phases of WAT development, an effect that strongly associates with Vstm2a expression.