par Bui, Le ;Menchi, Elena ;Blockx, Marie-Camille ;Denis, Olivier ;Delporte, Cédric ;Amighi, Karim ;Wauthoz, Nathalie
Référence Drug Delivery to the Lungs (35: 2024/12/11 - 2024/12/13: Edinburgh, Scottland)
Publication A Paraître, 2025
Poster de conférence
Résumé : Introduction. Inhaled corticosteroids (ICS) such as budesonide (BUD) are the cornerstone maintenance treatment for asthma. However, adherence to ICS therapy for chronic use can be challenging for patients. Poor adherence to inhaled medications increases with the frequency of administration, side effects, and erosion of inhalation technique. In this present study, pharmacokinetic profiles were determined for two innovative dry powders (DP) for inhalation presenting controlled BUD release with prolonged lung retention. Methods. BUD DPs were produced using a spray-drying particle engineering technique with different proportions of BUD (5% w/w or 20% w/w) and lipid matrix (95% and 80% w/w) comprising 1% tocopherol polyethylene glycol 1000 succinate (TPGS) and 99% hydrogenated castor oil (HCO). A pharmacokinetic study was performed on healthy rats, whereby plasma was collected at different timepoints after endotracheal administration of BUD-DPs. BUD was quantified using a validated LC-MS/MS method. Results. The DPs with HCO showed a controlled and sustained release after administration leading to a 9-fold higher tmax of 45 min versus 5 min and a 3-fold higher area under the curve (AUC) of 21.1 ± 2.4 ng.h/mL for BUD 5% (BH5.1) and 21.6 ± 1.5 ng.h/mL for BUD 20% (BH20.1) versus 8.5 ± 0.9 ng.h/mL for conventional micronized BUD (BH100). Conclusion. The innovative BUD DPs could be used at reduced dosage to increase BUD medication adherence by reducing BUD side effects, and/or at a frequency of administration from twice to once daily. These hypotheses will be then confirmed in a preclinical model of asthma in guinea pigs.

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