Pulmonary Department-Oncology Unit, G. Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Int J Pharm. 2013 Sep 10;453(2):480-7. doi: 10.1016/j.ijpharm.2013.06.011. Epub 2013 Jun 14.
Chemotherapy drugs have still the major disadvantage of non-specific cytotoxic effects. Although, new drugs targeting the genome of the tumor are already in the market, doublet chemotherapy regimens still remain the cornerstone of lung cancer treatment. Novel modalities of administration are under investigation such as; aerosol, intratumoral and intravascular.
In the present study five chemotherapy drugs; paclitaxel, docetaxel, gemcitabine, carboplatin and cisplatin were nebulized with three different jet nebulizers (Maxineb(®), Sunmist(®), Invacare(®)) and six different residual cups at different concentrations. The purpose of the study was to identify the "ideal" combination of nebulizer-residual cup design-drug-drug loading for a future concept of aerosol chemotherapy in lung cancer patients. The Mastersizer(®) 2000 was used to evaluate the aerosol droplet mass median aerodynamic diameter.
The drug, nebulizer and residual cup design greatly influences the producing droplet size (p<0.005, in each case). However; the design of the residual cup is the most important factor affecting the produced droplet size (F=834.6, p<0.001). The drug loading plays a vital role in the production of the desired droplet size (F=10.42, p<0.001). The smallest droplet size was produced at 8 ml loading (1.26 μm), while it remained the same at 2, 4 and 6 mls of drug loading.
The ideal nebulizer would be Maxineb(®), with a large residual cup (10 ml maximum loading capacity) and 8 mls loading and the drug with efficient pulmonary deposition would be docetaxel.
化疗药物仍然存在非特异性细胞毒性作用的主要缺点。尽管针对肿瘤基因组的新药已经上市，但双联化疗方案仍然是肺癌治疗的基石。新的给药方式正在研究中，如气雾剂、瘤内和血管内。
在本研究中，五种化疗药物；紫杉醇、多西他赛、吉西他滨、卡铂和顺铂分别用三种不同的射流雾化器（Maxineb®、Sunmist®、Invacare®）和六个不同的残留杯以不同的浓度进行雾化。本研究的目的是确定用于未来肺癌患者气雾剂化疗概念的“理想”雾化器-残留杯设计-药物-药物加载组合。Mastersizer®2000 用于评估气溶胶液滴质量中值空气动力学直径。
药物、雾化器和残留杯设计极大地影响产生的液滴大小（p<0.005，每种情况）。然而；残留杯的设计是影响产生液滴大小的最重要因素（F=834.6，p<0.001）。药物加载对产生所需液滴大小起着至关重要的作用（F=10.42，p<0.001）。在 8 毫升加载量时产生最小的液滴尺寸（1.26μm），而在 2、4 和 6 毫升药物加载量时保持不变。
理想的雾化器将是 Maxineb®，带有大容量残留杯（最大 10 毫升装量）和 8 毫升装量，具有高效肺部沉积的药物将是多西他赛。
