Insights into the pharmacokinetics, biodistribution, and oral toxicity of a polymeric benzimidazole – Curcumin nanocomplex with a multitarget anticancer potential

The current study investigates the oral toxicity of a PEGylated β-cyclodextrin-curcumin functionalized benzimidazole nanocomplex (BMPE-Cur) with multitarget anticancer potential in Swiss albino mice. Acute and chronic toxicities were evaluated after oral administration of BMPE-Cur in single doses ranging between 0.5 and 2.5 g/kg and repeated dosing of 5, 10, and 25 mg/kg for 28 consecutive days, respectively. Pharmacokinetic (PK) and biodistribution profiles of BMPE-Cur were analyzed by LC-MS. The toxicological assessments revealed that BMPE-Cur was tolerable up to 2.5 g/kg, with moderate organosomatic and biochemical alterations associated with doses >1.5 g/kg, whereas repeated dosing induced dose-dependent histopathological, hematological, and biochemical alterations. Doses within a range of 5–10 mg/kg were well tolerated, as indicated by the general normalization of the mentioned parameters. PK analysis revealed a similar value of maximum plasma concentration (C_max) attained by the free BMPE and BMPE-Cur. However, the latter accelerated the time to reach C_max (T_max) by 50 %, concomitant with longer residence time and lower clearance rate. BMPE-Cur also presented excellent hemocompatibility with human blood, with 46.58 %–99.96 % lower hemolysis than free BMPE within the same concentration range. These findings underscore the favorable pharmacokinetics and biocompatibility of BMPE-Cur while identifying safe therapeutic doses for potential human translation.