Wu Libo, Bharatwaj Balaji, Panyam Jayanth, da Rocha Sandro R P
Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan, USA.
Pharm Res. 2008 Feb;25(2):289-301. doi: 10.1007/s11095-007-9466-2. Epub 2007 Oct 17.
Demonstrate the applicability of a novel particle-based technology for the development of suspensions of small polar drugs and biomolecules in hydrofluoroalkane (HFA) propellants for pressurized metered-dose inhalers (pMDIs).
Emulsification diffusion was used to prepare core-shell particles. The shell consisted of oligo(lactide) grafts attached onto a short chitosan backbone. The active drug was arrested within the particle core. Colloidal Probe Microscopy (CPM) was used to determine the cohesive forces between particles in a model HFA propellant. The aerosol characteristics of the formulations were determined using an Anderson Cascade Impactor (ACI). Cytotoxicity studies were performed on lung epithelial and alveolar type II cells.
CPM results indicate that particle cohesive forces in liquid HFA are significantly screened in the presence of the polymeric shell and correlate well with the physical stability of suspensions in propellant HFA. The proposed formulation showed little or no cytotoxic effects on both Calu-3 and A549 cells.
Core-shell particles with a shell containing the lactide moiety as the HFA-phile showed excellent dispersion stability and aerosol characteristics in HFA-based pMDIs. This is a general strategy that can be used for developing novel suspension pMDIs of both small polar drugs and large therapeutic molecules.
证明一种基于新型颗粒技术在开发用于加压定量吸入器（pMDIs）的氢氟烷烃（HFA）推进剂中的小极性药物和生物分子悬浮液方面的适用性。
采用乳化扩散法制备核壳颗粒。壳层由连接在短壳聚糖主链上的低聚（丙交酯）接枝物组成。活性药物被截留在颗粒核心内。使用胶体探针显微镜（CPM）来测定模型HFA推进剂中颗粒之间的内聚力。使用安德森级联撞击器（ACI）测定制剂的气溶胶特性。对肺上皮细胞和II型肺泡细胞进行细胞毒性研究。
CPM结果表明，在聚合物壳层存在的情况下，液态HFA中的颗粒内聚力被显著屏蔽，并且与推进剂HFA中悬浮液的物理稳定性密切相关。所提出的制剂对Calu-3细胞和A549细胞几乎没有或没有细胞毒性作用。
具有含丙交酯部分作为亲HFA基团的壳层的核壳颗粒在基于HFA的pMDIs中显示出优异的分散稳定性和气溶胶特性。这是一种可用于开发小极性药物和大型治疗分子新型悬浮pMDIs的通用策略。
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