Al Hagbani Turki, Vishwa Bhavya, Abu Lila Amr S, Alotaibi Hadil Faris, Khafagy El-Sayed, Moin Afrasim, Gowda Devegowda V
Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia.
Department of Pharmaceutics, JSS College of Pharmacy, Mysuru 570015, India.
Pharmaceuticals (Basel). 2022 Apr 30;15(5):560. doi: 10.3390/ph15050560.
The objective of the current study was to develop poly (lactic-co-glycolic acid) (PLGA) microspheres loaded with the anti-tuberculosis (anti-TB) fluoroquinolone, Levofloxacin (LVX), in the form of dry powder inhalation (DPI). LVX-loaded microspheres were fabricated by solvent evaporation technique. Central Composite Design (CCD) was adopted to optimize the microspheres, with desired particle size, drug loading, and drug entrapment efficiency, for targeting alveolar macrophages via non-invasive pulmonary delivery. Structural characterization studies by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction analysis revealed the absence of any possible chemical interaction between the drug and the polymer used for the preparation of microspheres. In addition, the optimized drug-loaded microspheres exhibited desired average aerodynamic diameter of 2.13 ± 1.24 μm and fine particle fraction of 75.35 ± 1.42%, indicating good aerosolization properties. In vivo data demonstrated that LVX-loaded microspheres had superior lung accumulation, as evident by a two-fold increase in the area under the curve AUC, as compared with plain LVX. Furthermore, LVX-loaded microspheres prolonged drug residence time in the lung and maintained a relatively high drug concentration for a longer time, which contributed to a reduced leakage in the systemic circulation. In conclusion, inhalable LVX-loaded microspheres might represent a plausible delivery vehicle for targeting pulmonary tuberculosis via enhancing the therapeutic efficacy of LVX while minimizing its systemic off-target side effects.
本研究的目的是开发一种以干粉吸入剂（DPI）形式负载抗结核氟喹诺酮类药物左氧氟沙星（LVX）的聚乳酸-羟基乙酸共聚物（PLGA）微球。通过溶剂蒸发技术制备了负载LVX的微球。采用中心复合设计（CCD）优化微球，使其具有所需的粒径、载药量和药物包封率，以便通过无创肺部给药靶向肺泡巨噬细胞。通过差示扫描量热法（DSC）、傅里叶变换红外（FTIR）光谱和X射线衍射分析进行的结构表征研究表明，用于制备微球的药物与聚合物之间不存在任何可能的化学相互作用。此外，优化后的载药微球表现出所需的平均空气动力学直径为2.13±1.24μm，细颗粒分数为75.35±1.42%，表明具有良好的雾化性能。体内数据表明，与普通LVX相比，负载LVX的微球具有更好的肺部蓄积，曲线下面积AUC增加了两倍。此外，负载LVX的微球延长了药物在肺部的停留时间，并在较长时间内保持相对较高的药物浓度，这有助于减少体循环中的泄漏。总之，可吸入的负载LVX的微球可能是一种合理的给药载体，通过提高LVX的治疗效果同时最小化其全身非靶向副作用来靶向肺结核。
