| Autor: |
Craparo EF; Lab of Biocompatible Polymers, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy.; National Interuniversity Consortium for Materials Science and Technology (INSTM), UdR of Palermo, Via Giusti 9, 50125 Florence, Italy., Drago SE; Lab of Biocompatible Polymers, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy., Costabile G; Laboratory of Drug Delivery, Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy., Ferraro M; Institute of Translational Pharmacology (IFT), National Research Council of Italy (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy., Pace E; Institute of Translational Pharmacology (IFT), National Research Council of Italy (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy., Scaffaro R; National Interuniversity Consortium for Materials Science and Technology (INSTM), UdR of Palermo, Via Giusti 9, 50125 Florence, Italy.; Department of Engineering, University of Palermo, Viale delle Scienze, 90128 Palermo, Italy., Ungaro F; Laboratory of Drug Delivery, Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy., Cavallaro G; Lab of Biocompatible Polymers, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy.; National Interuniversity Consortium for Materials Science and Technology (INSTM), UdR of Palermo, Via Giusti 9, 50125 Florence, Italy.; Advanced Technology and Network Center (ATeN Center), University of Palermo, 90133 Palermo, Italy. |
| Abstrakt: |
Inhaled corticosteroids are the mainstay in the management of lung inflammation associated to chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Nonetheless, available inhalation products are mostly short-acting formulations that require frequent administrations and do not always produce the desired anti-inflammatory effects. In this work, the production of inhalable beclomethasone dipropionate (BDP) dry powders based on polymeric particles was attempted. As starting material, the PHEA-g-RhB-g-PLA-g-PEG copolymer was chosen, obtained by grafting 0.6, 2.4 and 3.0 mol%, respectively, of rhodamine (RhB), polylactic acid (PLA) and polyethylene glycol 5000 (PEG) on alpha,beta-poly(N-2-hydroxyethyl)DL-aspartamide (PHEA). The drug was loaded into the polymeric particles (MP) as an inclusion complex (CI) with hydroxypropyl-cyclodextrin (HP-β-Cyd) (at a stoichiometric ratio of 1:1) or as free form. The spray-drying (SD) process to produce MPs was optimized by keeping the polymer concentration (0.6 wt/vol%) constant in the liquid feed and by varying other parameters such as the drug concentration. The theoretical aerodynamic diameter (d aer ) values among the MPs are comparable and potentially suitable for inhalation, as confirmed also through evaluation of the experimental mass median aerodynamic diameter (MMAD exp ). BDP shows a controlled release profile from MPs that is significantly higher (more than tripled) than from Clenil ® . In vitro tests on bronchial epithelial cells (16HBE) and adenocarcinomic human alveolar basal epithelial cells (A549) showed that all the MP samples (empty or drug-loaded) were highly biocompatible. None of the systems used induced apoptosis or necrosis. Moreover, the BDP loaded into the particles (BDP-Micro and CI-Micro) was more efficient than free BDP to counteract the effects of cigarette smoke and LPS on release of IL-6 and IL-8. |
