Characterization of enteric-coated capsules filled with colchicine loaded zein nanoparticles for colon delivery

Abstract

Aim

In this study, we developed a dual pH and time-dependent formulation for targeted colonic release, aiming at minimizing adverse effect and enhancing anticancer efficacy of colchicine in the treatment of colorectal cancer.

Article highlights

The findings of this study confirmed that colchicine was successfully encapsulated into Z NPs.

The particle size of Col-Z NPs ranged from 79.7 to 173.0 nm with a PdI between 0.2 and 0.5. Factors such as polymer content, drug content, water-to-ethanol volume ratio, and ethanol concentration significantly influenced both particle size and PdI.

The EE% varied from 27.0% to 52.0%. Higher zein concentrations improved EE%, while an increased water-to-ethanol ratio decreased it.

The release profile of colchicine demonstrated a biphasic pattern at pH 7.4, characterized by an initial burst release followed by sustained release. The release was influenced by the water-to-ethanol ratio and ethanol concentration.

The cytotoxicity of optimized Col-Z NP was comparable to that of free colchicine at similar concentrations.

Enteric-coated capsules filled with Col-Z NP could protect the drug in the stomach (at pH 1.2) and gradually release the drug in the colon (at pH 7.4).

Materials and methods

To achieve this, colchicine was loaded in zein nanoparticles (Col-Z NP) which were further optimized and encapsulated in Eudragit S100 coated capsules. A full factorial design was employed to determine the optimal condition for preparation of Col-Z NP.

Results

The optimized Col-Z NPs exhibited a spherical shape with particle size of 104.3 ± 1.6 nm, polydispersity index of 0.27 ± 0.01, zeta potential of 29.0 ± 0.1 mV, encapsulation efficiency of 59.8 ± 4.8%, release efficiency over 8 h of 45.5 ± 2.7%, and drug loading of 13.0 ± 0.0%. No notable difference in cytotoxicity was observed between free colchicine and Col-Z NPs at comparable concentrations. The cellular uptake study showed more uptake for coumarin 6 loaded Z NPs compared to free coumarin 6. Colchicine release from coated capsules was restricted to around 3% in gastric medium and increased to about 8% in simulated intestine medium, respectively.