In vitro evaluation of nanoparticle formulations containing gangliosides

Due to their poor bioavailability after oral administration, the use of gangliosides in medicine is limited to the parenteral route of administration. In the present study, the association with poly(alkylcyanoacrylate) nanospheres and nanocapsules of monosialoganglioside GM1 and other chemically modified gangliosides was investigated with the aim of developing a colloidal drug delivery system suitable for use by the oral route. Our results show that gangliosides can be successfully associated with a biodegradable cyanoacrylic carrier either in the form of nanospheres or as nanocapsules, avoiding any degradation of the ganglioside molecule during the polymerization process. However, the drug-loading was found to be more efficient for nanocapsules. The amount of GM1 incorporated into nanospheres appeared to be dependent on the alkyl chain length of the cyanoacrylic polymer; this amount was however too low for pharmaceutical purposes. In contrast, nanocapsules allowed the attainment of very high drug encapsulation levels, especially with lipophilic derivatives of GM1, where an increase of lipophilicity has been obtained by chemical esterification of the sialic acid residue. Drug release experiments performed in the absence of enzymes indicated that nanocapsules were stable in acid medium, in which no drug release was observed, while their behaviour in basic medium was found to be affected by the composition of the oily phase and the oil/polymer ratio.