Assessing the Interaction between Dodecylphosphocholine and Dodecylmaltoside Mixed Micelles as Drug Carriers with Lipid Membrane: A Coarse-Grained Molecular Dynamics Simulation

Abstract

Integrating drugs into cellular membranes efficiently is a significant challenge in drug delivery systems. This study aimed to overcome these barriers by utilizing mixed micelles to enhance drug incorporation into cell membranes. We employed coarse-grained molecular dynamics (MD) simulations to investigate the stability and efficacy of micelles composed of dodecylphosphocholine (DPC), a zwitterionic surfactant, and dodecylmaltoside (DDM), a nonionic surfactant, at various mixing ratios. Additionally, we examined the incorporation of a mutated form of Indolicidin (IND) (CP10A), an anti-HIV peptide, into these micelles. This study provides valuable insights for the development of more effective drug delivery systems by optimizing the mixing ratios of DPC and DDM. By balancing stability and penetration efficiency, these mixed micelles can improve the delivery of drugs that face challenges crossing lipid membranes. Such advancements can enhance the efficacy of treatments for various conditions, including viral infections and cancer, by ensuring that therapeutic agents reach their intended cellular targets more effectively.

Figure 1

Comparison of R_g at Different Temperatures over a 300 ns simulation. The figure represents the variation in the R_g among different micelle systems at different temperatures. Micelles M75, M70, M40, M15, and M0 are represented in panels (a–e), respectively. Panel (f) presents a comparison of the radius of gyration for these five systems specifically at a temperature of 298.15 K.

Figure 2

Radial density profile of water in five different systems at a temperature of 298.15 K. Here, r denotes the distance from the CoM of the micelle.

Figure 3

(a) Structural drift, as measured by RMSD from the initial structure, against time for five micellar systems at 298.15 K, over a 300 ns simulation. (b) The figure shows the distances between the CoM of the micelles and CP10A. (c) The number of contacts between micelles and CP10A where their CoM distances from each other are less than 0.6 nm.

Figure 4

Interactions of CP10A with (a) M75, (b) M70, (c) M40, (d) M15, and (e) M0, as well as the depth of CP10A’s diffusion into these micelles at 298.15 K. Orange: DPC. Yellow: CP10A. Green: DDM.

Figure 5

RDF (ρ(r)) of water (depicted in black) and CP10A (depicted in red) for each system, calculated from the CoM of the micelles, at 298.15 K. (a) M75. (b) M70. (c) M40. (d) M15. (e) M0.

Figure 6

(a) APL of a mixed DPPC bilayer with 40% CHOL over a 300 ns simulation, (b) mass density.

Figure 7

Above: (side view) in each panel the snapshots were taken at various stages of the simulation during 8 ns at 298.15 K to indicate the best view of the interaction between the membrane and micelles, while either micelles or drugs are gradually drawn through the membrane. Below: (top view) the effect of diffusion process into the membrane perturbation. (a) M75. (b) M70. (c) M40. (d) M15. (e) M0. (f) CP10A.

Figure 8

MSD of five simulated systems at 298.15 K.

Figure 9

Energy profiles (kcal·mol^–1) of all the systems across the membrane as a function of the normal distance to the bilayer midplane (ξ(nm)) at 298.15 K.