Coadsorption of Doxorubicin and Selected Dyes on Carbon Nanotubes. Theoretical Investigation of Potential Application as a pH-Controlled Drug Delivery System

Abstract

This work shows results of a theoretical survey, based on molecular dynamics simulation, of potential applicability of doxorubicin coadsorption with various dyes molecules on/in carbon nanotubes as a drug delivery system. The central idea is to take advantage of the dyes charge distribution change upon switching the pH of the environment from neutral (physiological 7.4) to acidic one (∼5.5 which is typical for tumor tissues). This work discusses results obtained for four dye molecules revealing more or less interesting behavior. These were bromothymol blue, methyl red, neutral red, and p-phenylenediamine. All of them reveal pKa in the range 5-7 and thus will undergo protonation in that pH range. We considered coadsorption on external walls of carbon nanotubes and sequential filling of the nanotubes inner hollow space by drug and dyes. The latter approach, with the application of neutral red and p-phenylenediamine as blockers of doxorubicin, led to the most promising results. Closer analysis of these systems allowed us to state that neutral red can be particularly useful as a long-term blocker of doxorubicin encapsulated in the inner cavity of (30,0) carbon nanotube at neutral pH. At acidic pH we observed a spontaneous release of neutral red from the nanotube and unblocking of doxorubicin. We also confirmed, by analysis of free energy profiles, that unblocked doxorubicin can spontaneously leave the nanotube interior at the considered conditions. Thus, that system can realize pH controlled doxorubicin release in acidic environment of tumor tissues.

Carbon Nanotubes: Molecular and Electronic Properties of Regular and Defective Structures

“…In addition to the chirality, the diameter and length of the nanotube affect the nanotube-H 2 interactions. The diameter changes cause the variation in the nanotube curvature affecting the arrangement of the molecular orbitals [4], and the nanotube length variation affects the diffusivity as was determined for drug adsorption [52]. E ph values decrease for nanotubes with a smaller diameter and a larger length (higher number of carbon-atom layers) but increase with the number of adsorbed H 2 .…”

Recent advances in bioactive 1D and 2D carbon nanomaterials for biomedical applications

“…Panczyk et al has computationally shown that the chemotherapeutic drug doxorubicin (DOX) and several other hydrophobic dye molecules are readily adsorbed onto SWCNTs, and due to the protonation of the molecules at lower pH values, their release becomes favourable in low-pH environments that characterize tumor niches. 171 Exploiting this behaviour, Depan et al has shown that both DOX and folate-chitosan (a targeting molecule) can be loaded on GO sheets simply by mixing the two components with GO dispersed in aqueous solution. 172 DOX was released slowly in pH 5.3, but was retained in physiological pH 7.4.…”

Controlled Release of Doxorubicin from the Drug Delivery Formulation Composed of Single-Walled Carbon Nanotubes and Congo Red: A Molecular Dynamics Study and Dynamic Light Scattering Analysis

“…In addition, modeling of DOX interaction with some selected dyes (e.g., methyl red, neutral red, p-phenylenediamine and bromothymol blue) and carbon nanotubes has been described along with evaluation of the effect of lowered pH on drug release from such systems. The release of neutral red-DOX complex or free DOX from carbon nanotube surface was observed to occur after pH reduction [ 40 ]. However, to the best of our knowledge, there are no papers describing molecular dynamics study of the interactions between SRLS creating characteristic ribbon-like structures, taking CR as an example since it forms unique CR-DOX complexes with carbon nanotubes.…”