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.