Co-encapsulation of chloroquine plus colchicine in cationic nanocapsule suspensions: Technological development and toxicological evaluation

Abstract

This study aimed to co-nanoencapsulate chloroquine (CQ) and colchicine (CC) and evaluate the toxicity of the drug combination as a potential treatment for malaria. A pre-formulation chemical compatibility study was carried out to evaluate the feasibility of co-nanoencapsulation of drugs with excipients. Nanocapsules containing CQ + CC (1 + 0.5 mg/mL, respectively) were prepared with Eudragit RS®100 and developed using the nanoprecipitation method and then characterized. The in vitro release of the drug was tested at pH 7.4 using a dialysis bag, and acute in vivo toxicity was evaluated at doses of 5 and 20 mg/kg of CQ and 2.5 and 10 mg of CC, with free solution and nanoformulation groups, in male Wistar rats. Locomotor activity, motor coordination, leukocyte count, biochemical profile, tissue oxidative stress, histopathology, and relative weight of all organs were determined. Differential scanning calorimetry and thermogravimetric analyses revealed minimal interaction between drugs and the excipients. Cationic nanocapsules presented 238 ± 6 nm, +15.8 ± 1.1 mV, and 4.6 ± 0.1 pH and drug content (%) close to theoretical values, remaining stable for 90 days. The nanoencapsulation controlled the release of both drugs, showing a biexponential kinetics. No signs of toxicity were observed in animals treated with free or nanoencapsulated drugs at both doses. Therefore, the co-nanoencapsulated CQ plus CC is a promising candidate for antimalarial testing.