Co-polymeric hydrophilic nanospheres for drug delivery: Release kinetics, and cellular uptake.

ABSTRACT

Nanobiotechnology focuses on the biological effects and applications of nanoparticles that include nano-safety, drug encapsulation and nanotherapeutics. The present study focuses on hydrophilic nanospheres of copolymers N-isopropylacrylamide [NIPAAM] and vinyl pyrrolidone [VP], encapsulating a bioactive derivative of 5-fluorouracil-hexyl-carbamoyl fluorouracil (HCFU). The size of the nanospheres was ~58 nm and the surface charge measured was -15.4 mV. Under optimal conditions, the yield was >80%, and the drug loading was 2%. The entrapment efficiency was ~75%. Wide-angle X-ray diffraction analysis showed that the entrapped HCFU was present in an amorphous state, which has higher water solubility compared with the crystalline state. Slow drug release from nanospheres was observed in PBS and serum, with ~80% released at 37°C after 72 h. The HCFU loaded polymeric nanospheres have been found to be stable in whole blood having negligible RBC toxicity. Cytotoxicity in Mia-Paca 3, pancreatic cancer cell line was done in a 24-72 h assay. Dose dependant cytotoxicity was observed when incubated with various concentrations of HCFU loaded polymeric nanospheres while HCFU per se (<1 mg) showed 90% toxicity within 24 h.