Thermally responsive core-shell nanoparticles self-assembled from cholesteryl end-capped and grafted polyacrylamides:; drug incorporation and in vitro release.
The thermally responsive cholesteryl end-capped poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and cholesteryl grafted poly[N-isopropylacrylamide-co-N-(hydroxymethyl) acrylamide] amphiphilic polymers were synthesized and utilized to encapsulate cyclosporin A (CyA) and indomethacin (IND) within core-shell nanoparticles by a membrane dialysis method. The blank and drug-loaded nanoparticles were characterized using various analytical tools. The blank nanoparticles had a mean diameter less than 100 nm, whereas the drug-loaded nanoparticles were between 100 and 200 nm in diameter. The CAC value of cholesteryl end-capped and grafted polymers in PBS (pH 7.4) was estimated to be 16 and 8.5mg/l, respectively. The LCST value for both nanoparticle systems in PBS (pH 7.4) was determined to be 33.4 degrees C and 38.3 degrees C, respectively. The presence of proteins in PBS reduced the LCST. The core-shell nanoparticles provided great capacity for drug loading. In particular, the cholesteryl grafted polymer yielded a higher encapsulation efficiency for drugs. Compared to CyA, better entrapment was observed for IDN. A reduced fabrication temperature provided greater drug encapsulation efficiency. An increase in the initial drug content yielded lower drug encapsulation efficiencies at 10 degrees C and 15 degrees C. Increasing the polymer concentration increased drug encapsulation efficiency. The drug-loading process was analyzed to understand the effect of various fabrication parameters on drug encapsulation efficiency. IND release from the nanoparticles was responsive to temperature changes, being faster at a temperature around the LCST than below the LCST.
Chaw
Cheng-Shu
CS
Institute of Bioengineering and Nanotechnology, 1 Science Park Road, #01-01/10, The Aries, Singapore Science Park II, Singapore 117586, Singapore.
Chooi
Kar-Wai
KW
Liu
Xue-Ming
XM
Tan
Cherng-Wen
CW
Wang
Lin
L
Yang
Yi-Yan
YY
D000180:Acrylic Resins / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry*; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006358:Hot Temperature; D007213:Indomethacin / Q000008:administration & dosage* / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry* / Q000528:radiation effects / Q000648:ultrastructure; D010316:Particle Size
D000180:Acrylic Resins; C403811:poly(IPAAm-co-DMAAm); C052970:poly-N-isopropylacrylamide; D016572:Cyclosporine; D002784:Cholesterol; D007213:Indomethacin