Gelation microneedle (GMNs) based vaccinations with tumor antigens have been considered to be an attractive method for transcutaneous immunization because of their superior ability to deliver vaccines through the stratum corneum (SC) in a minimally invasive manner, which subsequently induces adaptive antitumor immunity. In this study, molecular dynamics (MD) uniaxial tension simulations were conducted to predict the formulation of poly(vinyl alcohol) (PVA; possesses high water solubility) and poly(methyl vinyl ether-altmaleic anhydride) (PMVEMA; possesses high mechanical strength) blend that has the strongest mechanical properties. To validate the accuracy of the Dreiding potential for these two polymers, their densities and Hildebrand solubility parameters were first predicted using MD simulations. These values exhibited good agreement with the corresponding experimental results, indicating the accuracy of the Dreiding potential for the polymers. Regarding the simulation results, the number density of H-bonds between PVA and PMVEMA was the highest at 50% PMVEMA, which can significantly enhance the mechanical strength of pristine PVA for enhanced skin immunization. In terms of further experimental validation, evidence from mechanical strength, solubility, in vitro porcine skin penetration tests, and in vivo immunization were consistent with our simulation predictions. In addition, our results indicated that delivery of ovalbumin (OVA) using GMN patches fabricated using PVA/PMVEMA (50%/50%) provided even stronger immune responses. Using this molecular simulation procedure, the optimal fraction of PVA/PMVEMA composite for the strongest mechanical properties can be rapidly predicted to reduce research time and costs in related experiments.
Keywords: microneedle patch; molecular dynamics simulation; ovalbumin antigen; polymer composites; sustained vaccine release.