Multiscale simulations of drug distributions in polymer dissolvable microneedles

Drug distribution in polymer dissolvable microneedles (MNs) is essential for enhancing the efficiency of drug delivery. In the present work, multiscale simulation was applied to study the interactions between polymer and drug molecules, which may influence the drug distribution in the MNs. In this study, Hyaluronic acid (HA) and Polyvinyl alcohol (PVA) were used to fabricate the MNs and sulfonhodamine B (SRB) was selected as the model drug. Firstly, from the quantum chemical calculations, the global electronegativity of HA (3.786 eV) is stronger than that of PVA (2.435 eV), which means that HA owns stronger electronegativity. The Flory-Huggins parameter of HA-SRB is -1.16 which is lower than that of PVA-SRB (53.51), indicating that HA has better compatibility with SRB molecules than PVA. From molecular dynamic simulations, the binding energy of HA-SRB is 93.52 kcal/mol which is much higher than that of PVA-SRB (-2.40 kcal/mol), meaning that HA is easier than PVA to combined with SRB. The mesoscale-based dissipative particle dynamics (DPD) simulations were applied to visualize the diffusion behavior of SRB and the swelling properties of the polymers. All the results indicated that SRB has a lower diffusion coefficient in PVA solution than that in HA solution, which may prevent the diffusion of drug from MN tips to the bases, facilitating the fabrication of MNs with drug concentrated MN tips. Finally, the SRB loaded PVA and HA MNs were prepared and the experimental results are consisted with the simulation results.