title: Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).
abstract: BACKGROUND
  Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery.
  
  
  RESULTS
  The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146-199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles.
  
  
  CONCLUSIONS
  This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.
authors.affiliation: The Center of General Education, Chang Gung University, Kweishan, Taoyuan, Taiwan. shen21@mail.cgu.edu.tw.
authors.forename: Ren-Shen
authors.initials: RS
authors.lastname: Lee
authors.affiliation: Center for General Education, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan. chlin@mail.cgust.edu.tw.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. ialjuffali@ksu.edu.sa.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, 333, Taiwan. jane2707@kimo.com.
authors.forename: Kai-Yin
authors.initials: KY
authors.lastname: Hu
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, 333, Taiwan. fajy@mail.cgu.edu.tw.|Immunology Consortium, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan. fajy@mail.cgu.edu.tw.|Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan. fajy@mail.cgu.edu.tw.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage* / Q000737:chemistry*; D000328:Adult; D000818:Animals; D002208:Caproates / Q000737:chemistry; D016190:Carboplatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007783:Lactones / Q000737:chemistry; D008168:Lung / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008823:Micelles; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014018:Tissue Distribution
chemical_list: D000180:Acrylic Resins; D002208:Caproates; D004337:Drug Carriers; D007783:Lactones; D008823:Micelles; D011091:Polyesters; C000609724:poly(N-isopropylacrylamide)-block-poly(epsilon-caprolactone); C121056:caprolactone; D016190:Carboplatin; D007770:L-Lactate Dehydrogenase