Interfacial encapsulation and desorption of mRNA in dual-oil systems

Liquid-liquid systems play an important role in chemical engineering processes, including the separation and handling of biomolecules. In this work, dissipative particle dynamics (DPD) simulations were employed to investigate the desorption and encapsulation behavior of messenger ribonucleic acid (mRNA-like) in a water-dual-oil system. Using diethyl phthalate (DEP) as an oil phase with low affinity toward the mRNA-like molecule, the effect of introducing a second solvent with strong affinity toward the mRNA-like molecule (good-oil) was systematically examined. The influence of good-oil volume fraction and mRNA-good-oil interaction parameters on interfacial partitioning and desorption was analyzed. Based on enthalpy-entropy considerations, desorption was found to become thermodynamically unfavorable when the favorable enthalpic interactions between the mRNA-like molecule and the good-oil, together with combinatorial entropic gains, could not compensate for the loss of conformational entropy. The effect of replacing DEP with other mRNA-repelling oils was also investigated. While the identity of the poor oil alters the interfacial position of the macromolecule, the feasibility of desorption and encapsulation is primarily governed by the good-oil fraction and the strength of mRNA-good-oil interactions. Based on these results, a phase map relating system conditions to the feasibility of the encapsulation of the mRNA-like molecule was constructed. Additionally, phase segregation and morphology during desorption were analyzed, revealing a transition from dispersed to stratified regimes as the good-oil fraction increased.