Sustained release of 5-fluorouracil from polymeric nanoparticles

The use of biodegradable nanoparticles loaded with 5-fluorouracil was inves tigated as a potential means to sustain the release of this drug. Nanoparti cles prepared from four biodegradable polymers were loaded with 5-fluoroura cil using three loading concentrations of drug and three different concentr ations of added polymer. Washing particles using a centrifugation/re-suspension with ultrasound prot ocol was found to dislodge the majority of drug, resulting in an over-estim ation of incorporation efficiency and low levels of strongly entrapped drug . Increasing the initial 5-fluorouracil concentration before polymer/monome r addition increased the drug loading in both washed and unwashed particles . Increasing the amount of polymer used to make nanoparticles did not incre ase loadings, but did produce increased amounts of unusable polymer waste. Drug release from nanoparticles was evaluated using a Franz cell diffusion apparatus, which showed an initial burst effect followed by a slower releas e phase over 24 h. Indeed, nanoparticles prepared from poly(lactide-co-glyc olide) released 66% of their 5-fluorouracil payload over this period. It was concluded that 5-fluorouracil-loaded nanoparticles could be readily included into a hydrogel-based delivery system to provide sustained drug re lease for trans-epithelial drug-delivery applications.