Formulation development and toxicological assessment of colchicine-loaded nanocapsules

Abstract

This study developed and characterized colchicine (COL) loaded-anionic nanocapsules prepared with poly(Ɛ-caprolactone) (NC-COL) and assessed their nanotoxicity in female Wistar rats, as per OECD Guideline 423, and C. elegans. The preformulation studies conducted using the components did not indicate any changes, implying compatibility in both the binary mixtures and the final formulation at temperatures below 100 °C. Blank nanocapsules (NC-B) and NC-COL nanocapsules exhibited sizes below 200 nm, monodisperse distribution, and high encapsulation efficiency (∼100 %). NC-B was significantly smaller than NC-COL, with all parameters remaining stable except for a slight reduction in pH over time. The in vitro COL release study showed that nanoencapsulation allows for the sustained bi-exponential release of COL. When exposed to the nanoencapsulated drug, C. elegans exhibited reduced survival rates, ranging from roughly 10–30 % at concentrations of 0.1 and 0.15 mg mL⁻¹, respectively. Acute oral toxicity studies in rats showed no histological, oxidative, or biochemical damage at the tested doses of NC-COL, although triglyceride levels decreased at the highest dose of COL (10 mg kg⁻¹). Our study successfully developed and characterized NC-COL, demonstrating its stability and controlled release properties. Despite the negative impact on C. elegans survival rates at higher doses, the rats did not exhibit adverse effects, regardless of the NC-COL dose, suggesting its potential safety for oral administration in therapeutic settings.