Guzmán Elisa A Torrico, Sun Qihua, Meenach Samantha A
University of Rhode Island, College of Engineering, Department of Chemical Engineering, 360 Fascitelli Center of Advanced Engineering, 2 Upper College Road, Kingston, RI 02881, USA.
University of Rhode Island, College of Pharmacy, Department of Biomedical and Pharmaceutical Sciences, Avedisian Hall, 7 Greenhouse Road, Kingston, RI 02881, USA.
ACS Biomater Sci Eng. 2019 Dec 9;5(12):6570-6580. doi: 10.1021/acsbiomaterials.9b00947. Epub 2019 Oct 23.
Paclitaxel (as intravenous Taxol) is one of the most applied chemotherapeutics used for the treatment of lung cancer. This project involves the development of a dry powder nanocomposite microparticle (nCmP) aerosol containing PTX-loaded nanoparticles (NP) to be delivered via a dry powder inhaler to the lungs for the treatment of non-small cell lung cancer (NSCLC). Nanoparticles were formulated by a single emulsion and solvent evaporation method, producing smooth, neutral PTX NP of approximately 200 nm in size. PTX nCmP were obtained via spray drying PTX NP with mannitol, producing amorphous wrinkled particles that demonstrated optimal aerosol deposition for pulmonary delivery. Free PTX, PTX NP, and PTX nCmP were evaluated in both 2D monolayers and 3D multicellular spheroids (MCS). PTX NP enhanced cytotoxicity when compared to pure drug in the 2D evaluation. However, on a liquid culture 3D tumor spheroid model, PTX NP and pure PTX showed similar efficacy in growth inhibition of MCS. The PTX nCmP formulation had a comparable cytotoxicity impact on MCS compared with free PTX. Finally, PTX nCmP were evaluated in an air-grown 3D MCS platform that mimics the pulmonary environment, representing a new model for the assessment of dry powder formulations.
紫杉醇（静脉注射用泰素）是治疗肺癌最常用的化疗药物之一。该项目涉及开发一种干粉纳米复合微粒（nCmP）气雾剂，其包含负载紫杉醇（PTX）的纳米颗粒（NP），通过干粉吸入器递送至肺部用于治疗非小细胞肺癌（NSCLC）。纳米颗粒通过单乳液和溶剂蒸发法制备，得到尺寸约为200 nm的光滑、中性的PTX纳米颗粒。PTX nCmP通过将PTX纳米颗粒与甘露醇喷雾干燥获得，产生无定形皱纹颗粒，其表现出用于肺部递送的最佳气溶胶沉积。在二维单层和三维多细胞球体（MCS）中对游离PTX、PTX纳米颗粒和PTX nCmP进行了评估。在二维评估中，与纯药物相比，PTX纳米颗粒增强了细胞毒性。然而，在液体培养的三维肿瘤球体模型中，PTX纳米颗粒和纯PTX在抑制MCS生长方面显示出相似的疗效。与游离PTX相比，PTX nCmP制剂对MCS具有相当的细胞毒性影响。最后，在模拟肺部环境的气生三维MCS平台上对PTX nCmP进行了评估，该平台代表了一种评估干粉制剂的新模型。
