Poly (N-isopropylacrylamide)-PLA and PLA blend nanoparticles for temperature-controllable drug release and intracellular uptake

被引:67
作者
Ayano, Eri [1 ]
Karaki, Miyuki [1 ]
Ishihara, Tsutomu [2 ]
Kanazawa, Hideko [1 ]
Okano, Teruo [3 ]
机构
[1] Keio Univ, Fac Pharm, Minato Ku, Tokyo 1058512, Japan
[2] Nihon Univ, Coll Engn, Koriyama, Fukushima 9638642, Japan
[3] Tokyo Womens Med Univ, TWIns, Inst Adv Biomed Engn & Sci, Shinjuku Ku, Tokyo 1628666, Japan
关键词
Temperature-responsive polymer; Poly (N-isopropylacrylamide); Poly (lactic acid); Nanoparticle; Cellular uptake; ACCELERATED BLOOD CLEARANCE; POLYMERIC MICELLES; PEGYLATED LIPOSOMES; MOLECULAR DESIGN; SURFACE-DENSITY; CELLULAR UPTAKE; GENE DELIVERY; CHAIN-LENGTH; PEG; CHROMATOGRAPHY;
D O I
10.1016/j.colsurfb.2011.10.003
中图分类号
Q6 [生物物理学];
学科分类号
071011 [生物物理学];
摘要
We designed a temperature-responsive and biodegradable novel drug-delivery carrier. A block copolymer, poly (N-isopropylacrylamide-DL-lactide) (PNIPAAm-PLA), was synthesized by the ring-opening polymerization of DL-lactide, and used as a carrier for a drug-delivery system. In this study, temperature-responsive nanoparticles (NPs) encapsulating betamethasone disodium 21-phosphate (BP) were prepared from a blend of PLA homopolymer and block copolymers by an oil-in-water solvent-diffusion method in the presence of zinc ion (PLA/PNIPAAm-PLA (NPs)). The resulting NP size was around 140 nm. The drug release from temperature-responsive NP could be controllable by changing the temperature. Moreover, a murine macrophage-like cell line, RAW 264.7 cells, was used to measure and image the cell uptake of fluorescent PLA/PNIPAAm-PLA NPs at 30 degrees C and 37 degrees C on the boundary of LCST (34 degrees C). Below the LCST, cellular uptake was not observed, but contrary to cellular uptake it was clearly observed above the LCST. Moreover, we found this effect to be useful for controlling the stealthiness by changing the temperature. Present temperature-responsive NPs have successfully exhibited thermo-responsive drug release and intracellular uptake while possessing a biodegradable character. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:67 / 73
页数:7
相关论文
共 59 条
[1]
Molecular Design of Outermost Surface Functionalized Thermoresponsive Polymeric Micelles with Biodegradable Cores [J].
Akimoto, Jun ;
Nakayama, Masamichi ;
Sakai, Kiyotaka ;
Okano, Teruo .
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 2008, 46 (21) :7127-7137
[2]
Thermally Controlled Intracellular Uptake System of Polymeric Micelles Possessing Poly(N-isopropylacrylamide)-Based Outer Coronas [J].
Akimoto, Jun ;
Nakayama, Masamichi ;
Sakai, Kiyotaka ;
Okano, Teruo .
MOLECULAR PHARMACEUTICS, 2010, 7 (04) :926-935
[3]
Temperature-Induced Intracellular Uptake of Thermoresponsive Polymeric Micelles [J].
Akimoto, Jun ;
Nakayama, Masamichi ;
Sakai, Kiyotaka ;
Okano, Teruo .
BIOMACROMOLECULES, 2009, 10 (06) :1331-1336
[4]
Effect of copolymer composition on the physicochemical characteristics, in vitro stability, and biodistribution of PLGA-mPEG nanoparticles [J].
Avgoustakis, K ;
Beletsi, A ;
Panagi, Z ;
Klepetsanis, P ;
Livaniou, E ;
Evangelatos, G ;
Ithakissios, DS .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2003, 259 (1-2) :115-127
[5]
Aqueous chromatography system using temperature-responsive polymer-modified stationary phases [J].
Ayano, E ;
Kanazawa, H .
JOURNAL OF SEPARATION SCIENCE, 2006, 29 (06) :738-749
[6]
Study of temperature-responsibility on the surfaces of a thermo-responsive polymer modified stationary phase [J].
Ayano, Eri ;
Okada, Yuji ;
Sakamoto, Chikako ;
Kanazawa, Hideko ;
Kikuchi, Akihiko ;
Okano, Teruo .
JOURNAL OF CHROMATOGRAPHY A, 2006, 1119 (1-2) :51-57
[7]
TEMPERATURE-DEPENDENCE OF SWELLING OF CROSS-LINKED POLY(N,N'-ALKYL SUBSTITUTED ACRYLAMIDES) IN WATER [J].
BAE, YH ;
OKANO, T ;
KIM, SW .
JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS, 1990, 28 (06) :923-936
[8]
STEALTH ME.PEG-PLA NANOPARTICLES AVOID UPTAKE BY THE MONONUCLEAR PHAGOCYTES SYSTEM [J].
BAZILE, D ;
PRUDHOMME, C ;
BASSOULLET, MT ;
MARLARD, M ;
SPENLEHAUER, G ;
VEILLARD, M .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1995, 84 (04) :493-498
[9]
Biodistribution properties of nanoparticles based on mixtures of PLGA with PLGA-PEG diblock copolymers [J].
Beletsi, A ;
Panagi, Z ;
Avgoustakis, K .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2005, 298 (01) :233-241
[10]
Thermo-responsive polymer nanoparticles with a core-shell micelle structure as site-specific drug carriers [J].
Cammas, S ;
Suzuki, K ;
Sone, C ;
Sakurai, Y ;
Kataoka, K ;
Okano, T .
JOURNAL OF CONTROLLED RELEASE, 1997, 48 (2-3) :157-164