Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone)

Journal of Nanobiotechnology

Research

Chih-Hung Lin¹  Ibrahim A Aljuffali²  Kai-Yin Hu³  Jia-You Fang⁴  Ren-Shen Lee⁵ 

[1] Center for General Education, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan;Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, 333, Taoyuan, Taiwan;Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, 333, Taoyuan, Taiwan;Immunology Consortium, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan;Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan;The Center of General Education, Chang Gung University, Kweishan, Taoyuan, Taiwan;

关键词: Copolymer;    Micelle;    Thermosensitivity;    Carboplatin;    Lung;    Passive targeting;   

DOI  :  10.1186/s12951-015-0103-7

 received in 2015-03-23, accepted in 2015-06-08,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAmphiphilic 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.ResultsThe 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.ConclusionThis study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

【 授权许可】

CC BY   
© Lee et al. 2015