Development of highly porous large PLGA microparticles for pulmonary drug delivery
Development of highly porous large PLGA microparticles for pulmonary drug delivery
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DOI：
10.1016/j.biomaterials.2008.12.044
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发表时间：
2009-04-01
期刊：
影响因子：
14
通讯作者：
Yeo, Yoon
中科院分区：
文献类型：
--
作者：
Yang, Yan;Bajaj, Nimisha;Yeo, Yoon
我们报告了一种制造高孔隙大型聚合物微粒的新工艺，用于通过吸入将局部药物输送到肺部。采用双乳化法制备聚乳酸-乙醇酸(PLGA)微粒(平均直径10-20μm)。为了赋予良好的空气动力学特性，内部水相中含有泡腾盐碳酸氢铵 (ABC)。当 ABC 以氨和二氧化碳形式逸出时，PLGA 颗粒中产生了高度多孔的结构。微粒的细颗粒分数 (FPF) 随着 ABC 与 PLGA 的比例而增加。当用 Anderson Cascade Impactor (ACI) 和 Rotahaler 进行测试时，用 7.5%w/w (ABC/PLGA) 制备的微粒的质量中值空气动力学直径 (MMAD) 为 4.0 +/- 1.2 μm，FPF 为 32.0 +/- 9.1 %。高孔隙度的大颗粒沉积在对应于气管及其下方的 ACI 阶段。高孔隙度的大颗粒避免了巨噬细胞的吞噬，而无孔的小颗粒则很快被巨噬细胞吞噬。与使用渗透原或可提取致孔剂的其他封装方法不同，该方法可以封装溶菌酶和阿霉素。 HCl，在 PLGA 微粒中具有高包封率（溶菌酶和阿霉素均接近 100%），其特征在于所需的 MMAD（4.5 +/- 0.6 μm 溶菌酶；4.6 +/- 0.4 μm 多柔比星）和 FPF（29.1 +/- 12.2% 溶菌酶；33.8 +/- 3.6%） 阿霉素）。 52% 的封装阿霉素在 4 天内从高孔微粒中释放出来。该方法是制造聚合物微粒以通过吸入持续局部给药的有效方法。 (C) 2008 Elsevier Ltd. 保留所有权利。
We report a new process of making highly-porous large polymeric microparticles for local drug delivery to the lungs by inhalation. Poly(lactic-co-glycolic acid) (PLGA) microparticles (average diameter, 10-20 mu m) were made by the double-emulsion method. To impart favorable aerodynamic properties, an effervescent salt ammonium bicarbonate (ABC) was included in the internal aqueous phase. ABC produced highly-porous structures in the PLGA particles as it escaped as ammonia and carbon dioxide. The fine-particle fraction (FPF) of the microparticles increased as a function of the ratio of ABC to PLGA. Microparticles prepared with 7.5%w/w (ABC/PLGA) had a mass median aerodynamic diameter (MMAD) of 4.0 +/- 1.2 mu m and FPF of 32.0 +/- 9.1 % when tested with Anderson Cascade Impactor (ACI) and Rotahaler. The highly-porous large particles deposited at the ACI stages corresponding to the trachea and below. The highly-porous large particles avoided phagorcytosis by macrophages, while non-porous small particles were quickly taken up by the macrophages. Unlike other encapsulation methods which employ osmogens or extractable porogens, this method could encapsulate lysozyme and doxorubicin. HCl, with high encapsulation efficiency (similar to 100% for both lysozyme and doxorubicin), in the PLGA microparticles characterized by desirable MMAD (4.5 +/- 0.6 mu m lysozyme; 4.6 +/- 0.4 mu m doxorubicin) and FPF (29.1 +/- 12.2% lysozyme; 33.8 +/- 3.6% doxorubicin). Fifty-two percent of encapsulated doxorubicin was released over 4 days from the highly-porous microparticles. This method is an efficient way of making polymeric microparticles for sustained local drug delivery by inhalation. (C) 2008 Elsevier Ltd. All rights reserved.