In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micro strategy was applied, encapsulating the nanoparticles in water-soluble mannitol-based microparticles by spray-drying. This process has allowed to produce spherical microparticles with the proper size for optimal lung deposition, and, once in contact with fluids mimicking the lung district, able to dissolve and release non-aggregated nanoparticles, potentially able to spread through the mucus, releasing about 70% of the drug payload in 24 h.

在本文中，通过接枝聚乳酸（PLA）作为疏水链和聚（2-甲基-2-恶唑啉）（PMeOx）或聚（2-甲基-2-恶嗪）（PMeOzi）作为亲水链，合成了两种两亲接枝共聚物。链分别连接到 α,β-聚 (N-2-羟乙基)-D,L-天冬酰胺 (PHEA) 的主链上。这些原始的接枝共聚物用于制备在吸入疗法中递送 Zileuton 的纳米颗粒。在各种测试方法中，直接纳米沉淀被证明是制备具有最小尺寸、最窄尺寸分布和球形的纳米粒子的最佳技术。为了克服吸入给药的尺寸限制，采用纳米到微米的策略，通过喷雾干燥将纳米颗粒封装在水溶性甘露醇基微粒中。