Bioadhesive properties of Gantrez nanoparticles.

Bioadhesive nanoparticles have been proposed as carriers for the oral delivery of poorly available drugs and facilitate the use of this route. This work summarises some experiments describing the bioadhesive potential of Gantrez nanoparticles fluorescently labeled with rhodamine B isothiocyanate. The adhesive potential of Gantrez was found to be stronger when folded as nanoparticles than in the solubilised form. Conventional nanoparticles displayed a tropism for the upper areas of the gastrointestinal tract, with a maximum of adhesion 30 min post-administration and a decrease in the adhered fraction along the time depending on the given dose. The cross-linkage of nanoparticles with increasing amounts of 1,3-diaminopropane stabilised the resulting carriers and prolonged their half-life in an aqueous environment; although, the adhesive capacity of nanoparticles, the intensity and the relative duration of the adhesive interactions within the gut as a function of the cross-linking degree. Finally, nanoparticles were coated with either gelatin or albumin. In the first case, the presence of gelatin dramatically decreased the initial capacity of these carriers to interact with the gut mucosa and the intensity of these phenomenons. In the latter, bovine serum albumin coated nanoparticles (BSA-NP) showed an important tropism for the stomach mucosa without further significant distribution to other parts of the gut mucosa.

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 BD-NP 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.