Agricultural Bio-pharmaceutical Laboratory, Qingdao Agricultural University, Qingdao, 266109, China.
National-Local Joint Engineering Laboratory of Agricultural Bio-pharmaceutical Technology, Qingdao, 266109, China.
Pharm Res. 2018 Feb 5;35(2):43. doi: 10.1007/s11095-018-2342-4.
The aim of this study was to prepare CEQ-loaded gelatin microspheres and compare two preparation methods, evaluate targeting to the lungs.
Gelatin microspheres containing CEQ were prepared by an emulsion cross-linking method (ECLM) and a spray-drying method (SDM) and were characterized in terms of morphology, size, drug-loading coefficient, encapsulation ratio and in vitro release.
The microspheres prepared by ECLM gave a drug loading (DL) of 19.4 ± 2.4% and an entrapment efficiency (EE) of 80.8 ± 3.2%. The microspheres prepared by SDM resulted in a DL value of 20.8 ± 2.7% and an EE of 95.3 ± 3.8%. The average particle size of microspheres was 7-30 μm by both methods and both preparations sustained CEQ release for 36 h in the target tissue (lungs). The in vitro release profile of the microspheres matched the Korsmeyer-Peppas release pattern. In vivo studies identified the lung as the target tissue and the region of maximum CEQ release. Histopathological examination showed a partial lung inflammation that disappeared spontaneously as the microspheres were biodegraded. In general, the formulations were safe.
The well-sustained CEQ release from the microspheres revealed its suitability as a drug delivery vehicle that minimized injury to healthy tissues while achieving the accumulation of therapeutic drug for lung targeting. The intravenous administration of CEQ gelatin microspheres prepared by SDM is of potential value in treating lung diseases in animals.
本研究旨在制备载 CEQ 的明胶微球，并比较两种制备方法，评估其对肺部的靶向性。
采用乳化交联法（ECLM）和喷雾干燥法（SDM）制备载 CEQ 的明胶微球，并对其形态、粒径、载药量、包封率和体外释放进行评价。
ECLM 法制备的微球载药量为 19.4±2.4%，包封率为 80.8±3.2%；SDM 法制备的微球载药量为 20.8±2.7%，包封率为 95.3±3.8%。两种方法制备的微球平均粒径均为 7-30 μm，均能在目标组织（肺部）中持续释放 36 h 的 CEQ。体外释放曲线符合 Korsmeyer-Peppas 释放模式。体内研究表明，肺部是微球的靶向组织和最大 CEQ 释放部位。组织病理学检查显示，微球具有部分肺部炎症，随着微球的生物降解，炎症会自行消失。一般来说，这些制剂是安全的。
微球能持续释放 CEQ，表明其适合作为一种药物传递载体，在实现肺部靶向治疗的同时，最大限度地减少对健康组织的损伤。SDM 法制备的 CEQ 明胶微球静脉给药，在治疗动物肺部疾病方面具有潜在价值。
