Nanoparticles with specific bioadhesive properties to circumvent the pre-systemic degradation of fluorinated pyrimidines

The aim was to evaluate the potential of specific bioadhesive nanoparticles to increase the oral bioavailability of pre-systemic degraded drugs, using 5-fluorouridine (FURD) as model. For this purpose, poly(methylvinylether-co-maleic anhydride) nanoparticles (NP), NP coated with albumin (BSA-NP) and NP treated with albumin and 1,3-diaminopropane (BD-NP) were used. All the formulations displayed a similar size and drug loading. However, BSA-NP showed a tropism for the stomach, NP developed adhesive interactions with both the stomach and middle portions of the small intestine and BDNP with the distal regions of the small intestine. These formulations were orally administered to laboratory animals and the FURD levels in plasma, tissues and urine were quantified at different times. From the urine data, the FURD bioavailability when loaded in either BSA-NP or NP was about 79% and 21%, respectively. For the control oral solution and BD-NP this parameter was 11% and 2%, respectively. FURD metabolism in gut was assessed by HPLC analysis of the lumen content. A FURD metabolite was found. Comparing the three nanoparticle formulations, the presence of the metabolite in the lumen contents was significantly higher for BD-NP than for NP and BSA-NP. In summary, the use of bioadhesive nanoparticles with tropism for the stomach mucosa may be considered as an adequate alternative to increase the bioavailability of some pre-systemic metabolised drugs. (C) 2004 Elsevier B.V. All rights reserved.