UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, UK.
Eur J Pharm Biopharm. 2012 May;81(1):74-81. doi: 10.1016/j.ejpb.2011.12.014. Epub 2012 Jan 9.
Crosslinked chitosan nanoparticles, prepared using ionic gelation, have been successfully formulated into pressurized metered dose inhalers (pMDIs) with potential for deep lung delivery of therapeutic agents. Nanoparticles were prepared from crosslinked chitosan alone and incorporating PEG 600, PEG 1000 and PEG 5000 for dispersion in aerosol propellant, hydrofuoroalkane (HFA) 227. Spherical, smooth-surfaced, cationic particles of mean size less than 230 nm were produced. Nanoparticles were positively charged and non-aggregated at the pH of the airways. Crosslinked chitosan-PEG 1000 nanoparticles demonstrated greatest dispersibility and physical stability in HFA-227, whereas other formulations readily either creamed or sedimented. Following actuation from pMDIs, the fine particle fraction (FPF) for crosslinked chitosan-PEG 1000 nanoparticles, determined using a next generation impactor, was 34.0±1.4% with a mass median aerodynamic diameter of 4.92±0.3 μm. The FPFs of crosslinked chitosan, crosslinked chitosan-PEG 600 and crosslinked chitosan-PEG 5000 nanoparticles were 5.7±0.9%, 11.8±2.7% and 17.0±2.1%, respectively. These results indicate that crosslinked chitosan-PEG 1000-based nanoparticles are promising candidates for delivering therapeutic agents, particularly biopharmaceuticals, using pMDIs.
交联壳聚糖纳米粒采用离子凝胶法制备，成功地制成了加压计量吸入器（pMDI），可将治疗剂递送到肺部深处。纳米粒由交联壳聚糖单独制备，并加入 PEG 600、PEG 1000 和 PEG 5000 以分散在气溶胶推进剂氢氟烷烃（HFA）227 中。产生了平均粒径小于 230nm 的球形、光滑表面、阳离子纳米粒。纳米粒在气道 pH 值下带正电荷且不聚集。交联壳聚糖-PEG 1000 纳米粒在 HFA-227 中表现出最大的分散性和物理稳定性，而其他制剂则容易出现乳膏或沉淀。从 pMDI 喷射后，使用下一代撞击器测定交联壳聚糖-PEG 1000 纳米粒的细颗粒分数（FPF）为 34.0±1.4%，质量中值空气动力学直径为 4.92±0.3μm。交联壳聚糖、交联壳聚糖-PEG 600 和交联壳聚糖-PEG 5000 纳米粒的 FPF 分别为 5.7±0.9%、11.8±2.7%和 17.0±2.1%。这些结果表明，交联壳聚糖-PEG 1000 基纳米粒是使用 pMDI 递送治疗剂，特别是生物制药的有前途的候选物。
