Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Drug Deliv. 2022 Dec;29(1):2058-2071. doi: 10.1080/10717544.2022.2092236.
Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of -31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.
哮喘是一种全球性的严重非传染性疾病,对儿科和成人都有重大的公共卫生影响,在严重情况下会引发大量的发病率和死亡率。β-肾上腺素受体激动剂硫酸特布他林(TBN)被用作支气管扩张剂来监测哮喘的发声症状。然而,TBN 口服给药相关的肝首过代谢会降低其临床疗效。同样,吸入 TBN 剂型的方案也限制了其应用。因此,这项工作关注的是将 TBN 纳入一种新型的非磷脂纳米囊泡给药系统,称为纳米囊泡(NVS),以便直接有效地将 TBN 靶向肺部。TBN-NVS 是根据薄膜水化法制备的,并采用 Box-Behnken 设计对制剂变量进行了统计学优化。此外,还通过级联撞击法研究了最佳 TBN-NVS 的空气动力学模式。还进行了使用大鼠模型的比较药代动力学研究。TBN 表现出高达 70%的包封效率。优化的 TBN-NVS 制剂显示平均纳米尺寸为 223.89nm,ζ 电位为-31.17mV,药物释放可持续长达 24 小时。此外,它在级联撞击器中表现出雪球状的肺部沉积行为,其中细颗粒分数为 86.44%。组织病理学研究证实了气管内给予 TBN-NVS 的安全性。药代动力学研究表明,与口服 TBN 溶液相比,最优 TBN-NVS 使 TBN 的生物利用度提高了 3.88 倍。简而言之,这些结果表明,NVS 是一种有前途的 TBN 肺部给药的纳米载体,由于具有靶向特异性,可全面控制疾病。