Preparation and Characterization of Nanoparticulate Poly(n‐isopropylacryl‐ Amide) Hydrogel for the Controlled Release of Anti‐tumour Drugs

BACKGROUND: Poly(N-isopropylacrylamide) (PNIPA) nanohydrogels were synthesized by inverse microemulsion to be used for the controlled release of anti-tumour drugs. Different methods were used to obtain drug-loaded xerogels, and their effect on drug release was studied, and evaluated using mathematical modelling.RESULTS: Nanoparticulate hydrogels, with a z-average diameter of 170 nm, were loaded with 5-fluorouracil (5-FU), mcthotrexate (MTX) or mitomycin C (MMC) by using spray drying (SD) and freeze drying (FD). Xerogels obtained by SD consisted of individual and independent particles, whereas particles established interactions in xerogels obtained by FD. Total drug release took place at 6 and 7 h from 5-FU-loaded and MMC-loaded xerogels prepared by SD, whereas MTX was expelled from the xerogels formed using the SD process. Drug release was slower from xerogels prepared by FD: 5-FU at 32 h, MMC at 120 h and MTX at 240 h. The Higuchi model most aptly fits the dissolution data. Non-Fickian and Fickian release behaviour can be attributed to SD and FD formulations, respectively.CONCLUSION: The amount of drug loaded, the morphology of xerogels as well as the drug release characteristics not only depend on the drug but also mainly on the process used to obtain the drug-loaded PNIPA xerogels. (C) 2008 Society of Chemical Industry