Halloysite nanotubes as carriers for irinotecan: Synthesis and characterization by experimental and molecular simulation methods

Halloysite, a clay mineral with spiral-shape tubular crystal morphology and biocompatibility with the human body, could be applied for the encapsulation of various bioactive molecules, serving as a controlled drug delivery nanocarrier. In this work, halloysite nanotubes have been investigated as a potential drug delivery system of irinotecan for colon cancer treatment administered by the oral route. The irinotecan-loaded halloysite nanotubes were coated with Eudragit S100 anionic copolymer in order to control and limit the drug release in the stomach pH while allowing it in the intestinal environment. The entrapment efficiency of the irinotecan in the halloysite nanotubes was very high, reaching 84.42 ± 3.10%. Transmission electron microscopy indicated that the drug molecules are located on the surface of the halloysite nanotubes and, as X-ray diffraction patterns confirmed, they were not positioned between the individual layers of halloysite nanotube. Thermogravimetric analysis indicated drug loading levels similar to that obtained spectrophotometrically and that the halloysite:polymer weight ratio in the polymer-coated samples was similar to the respective feed weight ratio (75:25). The drug release rate from the polymer-coated nanotubes was minimal (0.7% in 2 h) at stomach pH (pH 1.2) and high at intestinal pH 7.4 conditions (when the pH was increased to 7.4, drug release increased by approx. 70% in 2 h). The classical atomistic molecular simulation methods were used for the characterization of the mutual interactions in the modeled structure between the irinotecan cations and the halloysite nanotube at release pH value (pH 7.4). According to the geometry optimization results, the drug molecules (cations) remain closer to the outer part of the halloysite nanotubes. Longitudinal axes of the adjacent drug cations are positioned along the longitudinal axis of the tube and based on the calculations, these positions are energetically preferred. Based on molecular mechanics and molecular dynamics simulations, the preferred number of the drug cations loaded in a model of 5 ring-halloysite tube with a length of 25.359 Å is 6, and this number of cations is in agreement with the molar weight ratio of the components measured in real samples.