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 8.5 mg/l, respectively. The LCST value for both nanoparticle systems in PBS (pH 7.4) was determined to be 33.4degreesC and 38.3degreesC, 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 10degreesC and 15degreesC. 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. (C) 2003 Elsevier Ltd. All rights reserved.