NanoCipro encapsulation in monodisperse large porous PLGA microparticles
NanoCipro encapsulation in monodisperse large porous PLGA microparticles
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DOI：
10.1016/j.jconrel.2007.05.039
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发表时间：
2007-08-16
影响因子：
10.8
通讯作者：
Berkland, Cory
中科院分区：
文献类型：
--
作者：
Arnold, Matthew M.;Gonnan, Enic M.;Berkland, Cory
控制释放制剂的肺部药物递送可能为口服抗生素清除持续性肺部感染提供一种有效的辅助方法。用于该适应症的干粉制剂应具有以下特征：有效沉积至感染的肺室、在感染部位的持久性和抗生素的稳定释放。与小微粒（类似于1-5 μ m）相比，大的多孔颗粒（类似于10- 1-5 μ m）由于其大的直径和减少的巨噬细胞清除率而表现出有效的肺沉积和增强的肺驻留。在本报告中，使用精密颗粒制造技术，利用油作为可浸提致孔剂，制备聚（D，L-乳酸-羟基乙酸）（PLGA）的单分散大多孔颗粒。萃取后，所得的大的多孔PLGA颗粒表现出低密度和网状或中空的内部取决于致孔剂的浓度和类型，分别。通过在二氯甲烷中均质化产生的环丙沙星纳米颗粒（nanoCipro）具有熔融温度降低的多晶型物。将nanoCipro包封在大的多孔PLGA颗粒中导致环丙沙星的稳定释放，与大的多孔颗粒相比，环丙沙星的稳定释放对于较大的颗粒直径和固体颗粒形态是延长的。nanoCipro的包封率相当低，并阐明了在颗粒形成过程中影响纳米颗粒包封的因素。开发了一种具有控制颗粒沉积和持续释放到肺部的潜力的干粉制剂，并讨论了改善纳米颗粒包封的见解。由爱思唯尔公司出版
Pulmonary drug delivery of controlled release formulations may provide an effective adjunct approach to orally delivered antibiotics for clearing persistent lung infections. Dry powder formulations for this indication should possess characteristics including; effective deposition to infected lung compartments, persistence at the infection site, and steady release of antibiotic. Large porous particles (similar to 10-15 mu m) have demonstrated effective lung deposition and enhanced lung residence as a result of their large diameter and reduced clearance by macrophages in comparison to small microparticles (similar to 1-5 mu m). In this report, Precision Particle Fabrication technology was used to create monodisperse large porous particles of poly(D,L-lactic-co-glycolic acid) (PLGA) utilizing oils as extractable porogens. After extraction, the resulting large porous PLGA particles exhibited a low density and a web-like or hollow interior depending on porogen concentration and type, respectively. Ciprofloxacin nanoparticles (nanoCipro) created by homogenization in dichloromethane, possessed a polymorph with a decreased melting temperature. Encapsulating nanoCipro in large porous PLGA particles resulted in a steady release of ciprofloxacin that was extended for larger particle diameters and for the solid particle morphology in comparison to large porous particles. The encapsulation efficiency of nanoCipro was quite low and factors impacting the entrapment of nanoparticles during particle formation were elucidated. A dry powder formulation with the potential to control particle deposition and sustain release to the lung was developed and insight to improve nanoparticle encapsulation is discussed. Published by Elsevier B.V.