Effect of genotype and sex of the host on the bioavailability of novel albendazole microcrystals based on chitosan and cellulose derivatives

Abstract

Albendazole (ABZ), an anthelmintic compound widely used in the treatment of systemic nematode infections, is included in the list of class II drugs based on the Biopharmaceutical Classification System. ABZ has limited effectiveness due to its poor water solubility and consequent low bioavailability. Bioavailability of novel ABZ microcrystals based on hydroxyethylcellulose (S4A) or chitosan (S10A) was studied in male and female mice of two inbred lines, from the murine CBi-IGE model of trichinellosis, differing in susceptibility to this parasitosis (line CBi/L, resistant; line CBi+, susceptible). ABZ microcrystals were administered orally, and albendazole sulfoxide (ABZSO) was quantified in plasma by high-performance liquid chromatography. Mice given the microcrystals showed a significant increase in maximum plasmatic concentration (Cmax) compared with those receiving pure ABZ (P < 0.01). In both genotypes, males and females given S4A had higher Cmax than those receiving S10A (P < 0.05). CBi/L showed a greater Cmax than CBi+ (significantly different only in females treated with S4A (P 0 0.001)). CBi/L females attained a higher Cmax than males (P < 0.05). No sex effect was observed for this variable in CBi+ (P > 0.05). The results of the pharmacokinetic analysis indicate that the microcrystalline formulations optimize ABZ bioavailability, both in males and females, S4A being the best system in CBi/L mice and S10A in CBi+. In summary, the microcrystals increased ABZ bioavailability