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Nanoparticles have widely been studied in drug delivery research for targeting and controlled release. The aim of this article is application of nanoparticles as an inhalable agent for treatment of lung cancer. To deposit effectively deep the particles in the lungs, the PLGA nanoparticles loaded with the anticancer drug 6-{[2-(dimethylamino)ethyl]amino}-3-hydroxyl-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103) were prepared in the form of nanocomposite particles. The nanocomposite particles consist of the complex of drug-loaded nanoparticles and excipients. In this study, the anticancer effects of the nanocomposite particles against the lung cancer cell line A549. Also, the concentration of TAS-103 in blood and lungs were determined after administration of the nanocomposite particles by inhalation to rats. TAS-103-loaded PLGA nanoparticles were prepared with 5% and 10% of loading ratio by spray drying method with trehalose as an excipient. The 5% drug-loaded nanocomposite particles were more suitable for inhalable agent because of the sustained release of TAS-103 and higher FPF value. Cytotoxicity of nanocomposite particles against A549 cells was higher than that of free drug. When the nanocomposite particles were administered in rats by inhalation, drug concentration in lung was much higher than that in plasma. Furthermore, drug concentration in lungs administered by inhalation of nanocomposite particles was much higher than that after intravenous administration of free drug. From these results, the nanocomposite particle systems could be promising for treatment of lung cancer.

Nanoparticles are expected to be applicable to inhalation as carrier but there exist disadvantages because of their size. Their deposition dose to the lung will be small. To overcome this problem and utilize nanoparticles for inhalation, we have prepared nanocomposite particles as drug carriers targeting lungs. The nanocomposite particles are prepared as drug-loaded nanoparticles-additive complex to reach deep in the lungs and to be decomposed into nanoparticles when they deposit into lung. In this study, we examined the effect of preparation condition--inlet temperature, size of primary nanoparticles and weight ratio of primary nanoparticles--on the property of nanocomposite particles. When the size of primary nanoparticles was 400 nm and inlet temperature was 90 degrees C, only the nanocomposite particles containing between 45 and 55% of primary nanoparticles could be decomposed into nanoparticles in water. On the other hand, when the inlet temperature was 80 degrees C, nanocomposite particles were decomposed into nanoparticles independent of the weight ratio of primary nanoparticles. Also, the aerodynamic diameter of the nanocomposite particles was between 1.5 and 2.5 microm, independent of the weight ratio of primary nanoparticles. When the size of primary nanoparticles was 200 nm and inlet temperature was 70 degrees C, nanocomposite particles were decomposed into nanoparticles independent of the weight ratio of primary nanoparticles. Also, the aerodynamic diameters of them were almost 2.0 microm independent of the weight ratio of primary nanoparticles. When the nanocomposite particles containing nanoparticles with the size of 200 nm are prepared at 80 degrees C, no decomposition into nanoparticles was observed in water. Fine particle values, FPF, of the nanocomposite particles were not affected by the weight ratio of primary nanoparticles when they were prepared at optimum inlet temperature.

To overcome the disadvantages both of microparticles and nanoparticles for inhalation, we have prepared nanocomposite particles as drug carriers targeting lungs. The nanocomposite particles having sizes about 2.5 microm composed of sugar and drug-loaded PLGA nanoparticles can reach deep in the lungs, and they are decomposed into drug-loaded PLGA nanoparticles in the alveoli. Sugar was used as a binder of PLGA nanoparticles to be nanocomposite particles and is soluble in alveolar lining fluid. The primary nanoparticles containing bioactive materials were prepared by using a probe sonicator. And then they were spray dried with carrier materials, such as trehalose and lactose. The effects of inlet temperature of spray dryer were studied between 60 and 120 degrees C and the kind of sugars upon properties of nanocomposite particles. When the inlet temperatures were 80 and 90 degrees C, nanocomposite particles with average diameters of about 2.5 microm are obtained and they are decomposed into primary nanoparticles in water, in both sugars are used as a binder. But, those prepared above 100 degrees C are not decomposed into nanoparticles in water, while the average diameter was almost 2.5 microm. On the other hand, nanocomposite particles prepared at lower inlet temperatures have larger sizes but better redispersion efficiency in water. By the measurements of aerodynamic diameters of the nanocomposite particles prepared with trehalose at 70, 80, and 90 degrees C, it was shown that the particles prepared at 80 degrees C have the highest fine particle fraction (FPF) value and the particles are suitable for pulmonary delivery of bioactive materials deep in the lungs. Meanwhile the case with lactose, the particles prepared at 90 degrees C have near the best FPF value but they have many particles larger than 11 microm.