Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer.
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.
Tomoda
Keishiro
K
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Ohkoshi
Takumi
T
Hirota
Keiji
K
Sonavane
Ganeshchandra S
GS
Nakajima
Takehisa
T
Terada
Hiroshi
H
Komuro
Masahito
M
Kitazato
Kenji
K
Makino
Kimiko
K
D000280:Administration, Inhalation; D000634:Aminoquinolines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007192:Indenes / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley
D000634:Aminoquinolines; D007192:Indenes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C106647:6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one