Saafan Hesham A, Ibrahim Kamilia M, Thabet Yasmeena, Elbeltagy Sara M, Eissa Rana A, Ghaleb Ashraf H, Ibrahim Fathy, Elsabahy Mahmoud, Eissa Noura G
School of Biotechnology, Badr University in Cairo, Cairo 11829, Egypt.
Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32304, USA.
Pharmaceutics. 2021 Oct 14;13(10):1677. doi: 10.3390/pharmaceutics13101677.
Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr's index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100-150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.
肺部给药为口服和侵入性给药途径提供了一种有用的替代方法，同时增强并延长了药物在肺部的蓄积，并减少了全身药物暴露。在本研究中，作为模型药物的氯喹被载入脂质体，以便通过干粉吸入或气管内给药的方式进行潜在的肺部给药。已制备并广泛表征了载氯喹脂质体。此外，将载药脂质体冻干，并通过测量休止角、卡尔指数和豪斯纳比来评估其流动性。所开发的脂质体呈现出纳米尺寸（100 - 150 nm）的球形形态，氯喹包封率约为24.5%。傅里叶变换红外光谱（FT - IR）结果表明氯喹已载入脂质体，而体外释放研究表明与游离药物相比，载药脂质体具有缓释特性。冻干脂质体表现出较差的流动性，在添加乳糖后或在整个冻干过程中使用冷冻保护剂时，流动性没有得到充分改善。在体内，给大鼠气管内注射载氯喹脂质体后，血液中的药物浓度比口服游离药物低10倍。肺部给药载药纳米颗粒后，肾脏和肝脏功能的生物标志物（即肌酐、尿素、谷草转氨酶和谷丙转氨酶）水平与未治疗的对照动物相似。因此，不建议使用干粉吸入器来给药冻干脂质体，而气管内给药可能为脂质体分散体的肺部给药提供一种有前景的策略，同时将全身药物暴露和不良反应降至最低。
