Boyuklieva Radka, Katsarov Plamen, Zagorchev Plamen, Abarova Silviya, Hristozova Asya, Pilicheva Bissera
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
J Funct Biomater. 2024 Nov 5;15(11):329. doi: 10.3390/jfb15110329.
Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the other hand, when administered by an alternative route of administration, such as the nasal route, systemic exposure to deferiprone will be reduced, thereby reducing the occurrence of adverse effects. Direct nose-to-brain delivery has been raised as a non-invasive strategy to deliver drugs to the brain, bypassing the blood-brain barrier. The aim of the study was to develop and characterize nanocomposite microspheres suitable for intranasal administration by combining nano- and microparticle-based approaches. Nanoparticles with an average particle size of 213 ± 56 nm based on the biodegradable polymer poly-ε-caprolactone were developed using the solvent evaporation method. To ensure the deposition of the particles in the nasal cavity and avoid exhalation or deposition into the small airways, the nanoparticles were incorporated into composite structures of sodium alginate obtained by spray drying. Deferiprone demonstrated sustained release from the nanocomposite microspheres and high iron-chelating activity.
脑铁水平升高是许多神经退行性疾病的特征。去铁酮作为一种生物半衰期短的铁螯合剂，随着治疗疗程的延长会导致粒细胞缺乏症和中性粒细胞减少症。将其制成缓释剂型可能会减少给药频率。另一方面，当通过替代给药途径（如鼻腔途径）给药时，去铁酮的全身暴露会减少，从而降低不良反应的发生率。直接鼻-脑给药作为一种绕过血脑屏障将药物输送到大脑的非侵入性策略已被提出。本研究的目的是通过结合基于纳米和微粒的方法来开发和表征适合鼻腔给药的纳米复合微球。使用溶剂蒸发法制备了基于可生物降解聚合物聚ε-己内酯的平均粒径为213±56 nm的纳米颗粒。为了确保颗粒在鼻腔中的沉积并避免呼出或沉积到小气道中，将纳米颗粒掺入通过喷雾干燥获得的海藻酸钠复合结构中。去铁酮从纳米复合微球中显示出持续释放和高铁螯合活性。
