Interest of cyclodextrins in spray-dried microparticles formulation for sustained pulmonary delivery of budesonide
Interest of cyclodextrins in spray-dried microparticles formulation for sustained pulmonary delivery of budesonide
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DOI：
10.1016/j.ijpharm.2015.09.052
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发表时间：
2015-11-30
影响因子：
5.8
通讯作者：
Evrard, Brigitte
中科院分区：
文献类型：
--
作者：
Dufour, Gilles;Bigazzi, William;Evrard, Brigitte
为了达到有效的肺输送和疗效，活性成分的雾化特性和通过肺的渗透性都需要优化。为了克服这些挑战，目前的研究旨在开发含有治疗性皮质类固醇（布地奈德）的环糊精喷雾干燥微颗粒，可用于控制与哮喘相关的气道炎症。研究了布地奈德与羟丙基-环糊精（HPBCD）的络合作用。采用双流体喷嘴喷雾干燥机生产吸入性粉末，并在实验设计的基础上进行了优化。喷雾干燥的微颗粒显示出特定的“放气球状”，与吸入的适当大小相关。空气动力学评估表明，与经典的以乳糖为基础的布地奈德配方相比，细颗粒分数有所增加（44.05比26.24%）。此外，在环糊精复合物的存在下，布地奈德肺外通透性降低。这种持续布地奈德释放的兴趣在哮喘小鼠模型中进行了评估。与非络合布地奈德制剂在相同浓度下的抗炎效果进行了比较，证明了以环糊精为基础的制剂具有更高的抗炎活性。因此，这种策略对于提高肺部靶向性，同时减少与高剂量皮质类固醇相关的全身副作用具有特别的意义。综上所述，本研究报告表明，环糊精可用于粉末吸入，既能改善活性成分的雾化特性，又能进一步溶解在肺液中，减少肺外渗透性，从而优化活性谱。(C) 2015 Elsevier B.V.版权所有
To achieve an efficient lung delivery and efficacy, both active ingredient aerosolisation properties and permeability through the lung need to be optimized. To overcome these challenges, the present studies aim to develop cyclodextrin-based spray-dried microparticles containing a therapeutic corticosteroid (budesonide) that could be used to control airway inflammation associated with asthma. The complexation between budesonide and hydroxypropyl-beta-cyclodextrin (HPBCD) has been investigated. Production of inhalation powders was carried out using a bi-fluid nozzle spray dryer and was optimized based on a design of experiments. Spray-dried microparticles display a specific "deflated-ball like shape" associated with an appropriate size for inhalation. Aerodynamic assessment show that the fine particle fraction was increased compared to a classical lactose-based budesonide formulation (44.05 vs 26.24%). Moreover, the budesonide permeability out of the lung was shown to be reduced in the presence of cyclodextrin complexes. The interest of this sustained budesonide release was evaluated in a mouse model of asthma. The anti-inflammatory effect was compared to a non-complexed budesonide formulation at the same concentration and attests the higher anti-inflammatory activity reach with the cyclodextrin-based formulation. This strategy could therefore be of particular interest for improving lung targeting while decreasing systemic side effects associated with high doses of corticosteroids. In conclusion, this works reports that cyclodextrins could be used in powder for inhalation, both for their abilities to improve active ingredient aerosolisation properties and further to their dissolution in lung fluid, to decrease permeability out of the lungs leading to an optimized activity profile. (C) 2015 Elsevier B.V. All rights reserved.