Effect of Genotype and Sex of the Host on the Bioavailability of Novel Albendazole Microcrystals Based on Chitosan and Cellulose Derivatives

Effect of sex and genotype of the host on the anthelmintic efficacy of albendazole microcrystals, in the CBi-IGE Trichinella infection murine model

“…In recent years, several studies have described sex-related differences in the progression of diseases and the disposition of drugs in the body (Capece et al ., 2000; Afonso-Pereira et al ., 2018; Moyer et al ., 2019; Valodara and Sr, 2019). In a previous experiment analysing the pharmacokinetics of S4A and S10A (Codina et al ., 2020), ABZ bioavailability was significantly increased when administered as microcrystalline formulations. However, host genotype and sex influenced the pharmacokinetic parameters measured: CBi/L females attained a significantly higher C max compared to males, whereas no sex effect was observed for this variable in CBi+.…”

“…However, ABZ formulations commercially available have shown therapeutic failure in the chronic phase, and longer treatments and higher doses are required, enhancing the risk of side- effects. Modifying the properties of solid compounds through micro-crystallization of ABZ allowed us to obtain formulations with better biopharmaceutical properties and potential improved effectiveness (Priotti et al ., 2017; Codina et al ., 2020), the next step being to test their therapeutic efficacy in vivo in an animal model of T. spiralis infection. The Trichinella /mouse model has been widely used to assay benzimidazole carbamates' anthelmintic effectiveness (McCracken, 1978; López-García et al ., 1997; Chung et al ., 2001; Casulli et al ., 2006; García et al ., 2013; Codina et al ., 2015).…”

“…Formulations or ABZ powder were prepared and administered orally as previously described in detail by Codina et al . (2020).…”

“…In order to evaluate the efficacy of the treatment against the different stages of T. spiralis , ABZ and the microcrystal formulations S4A and S10A were administered orally in a single dose (30 mg ABZ per kg body weight per day), as already described (Codina et al ., 2020), at different stages of the parasite cycle (Fig. 1).…”

“…These studies showed that the microcrystalline systems based on hydroxyethyl-cellulose (S4A) and chitosan (S10A) were the best options to optimize oral absorption of the active pharmaceutical ingredient. Furthermore, the pharmacokinetics analysis, using two mouse lines that differ in susceptibility to T. spiralis , demonstrated that microcrystal formulations increased ABZ bioavailability and pharmacokinetic parameters were affected by the host sex and genotype (Codina et al ., 2020).…”