Molecular assembly of hyaluronic acid nanoparticles for drug delivery by molecular dynamics simulation

Abstract

Nanoparticles (NPs) offer a promising approach in modern medicine for the treatment of various diseases. They serve as effective carriers for various drugs including antibiotics, antivirals and anticancer agents. Hyaluronic acid-based nanoparticles (HA-NPs) have been interested owing to their exceptional biocompatibility and biodegradability. Hyaluronic acid (HA) is a natural biopolymer with versatile applications. However, there have been limited numbers of studies on molecular simulations of nanoparticles, particularly HA-NPs. In this study, molecular dynamics simulations were employed to explore molecular models representing the assembly of HA-NPs. Two types of HA-NPs, acetylated hyaluronic acid nanoparticles (AcHA-NPs) and hyaluronic acid-ceramide nanoparticles (HACe-NPs), were assessed for their stability and drug adsorption ability by varying the size and number of HA chains to form the nanoparticle under different conditions. The findings of the study revealed that the AcHA-NP model adopted a random or amorphous structure, whereas the HACe-NP exhibited a well-organized micelles-like structure. Both types of HA-NPs demonstrated potential drug carriers, as doxorubicin molecules were able to bind. It is important to note that AcHA-NP lacked of specific binding site due to its random structure whereas the drug clustered around the hydrophobic core of the HACe-NP.