(203g) Development of Drug Delivery Systems Based on a Fructose Polymer and 5-Fluorouracil

Alvaro G. Garcinuño, Antonio Tabernero, Miguel A. Galan, Eva M. Martin Del Valle

Department of Chemical Engineering. University of Salamanca.

There are new trends in biomedical engineering related with novel biomaterials which will be more compatible and more biodegradable than those that are being used at this time. For that reason, we use a polymer of fructose (levan) that has been successfully proved for forming nanocapsules by a self-assembled process.

Specifically, it is built a new drug delivery system (DDS) composed by levan and 5-fluouracil (a drug sometimes used in colorectal and hepatic cancer treatment). The work also presents results from a surface-modification of the initial levan (its carboxylate form).

The work shows how some parameters affect levan-nanoparticles synthesis, improving critical values such as size or Zpotential, in order to build a good DDS. The effect of pH and ionic strength are critical for nanoparticles assembly. Basic pHs are needed to obtain the best results (particle size between 300-400 nm with a Zpotential value around -20 mV). Those conditions avoid nanoparticle aggregation because the hydrocyl radicals of the medium take a hydrogen atom from the polymer that gets a negative charge. The ionic strength only affects the aggregation at high pHs (body blood ionic strength offers good results even at high pHs).

Moreover, carboxymethylation of the levan is performed to obtain carboxymethyllevan (CML). That surface-modification maintain good levels of size (between 300-400 nm), and improve Zpotential (-35 mV). That increment in Zpotential value prevents further particle aggregation, which is an interesting advantage for clinical or in vivo essays. Some studies of aggregation at different times were also performed. In both cases, at low ionic strength and basic pH, little aggregation was observed.

Results indicate that 5-fluorouracil is bound to either levan or CML surface by electrostatic interactions, obtaining the best results at basic pHs. According to drug release experiments, between 45-70% of the 5-fluoruracil is released from the levan in 23 hours depending on the pH, whereas only a low percentage of the drug is released at the initial times from the CML because of the stability of the amide bond that is produced on the surface. That fact emphasizes the good strategy of carboxymethylation for creating an effective drug delivery system.