(363i) Study of the Formation and Morphology of Biodegradable Polymeric Janus Particles Via Atomistic Simulation of Interfacial Interactions

Janus particles are defined as isotropic amphiphilic particles having different chemical or physical properties in two surface regions. Biocompatible or biodegradable polymeric Janus particles have many potential applications in drug delivery, such as acting as a stabilizer for nanocrystal drug suspensions or site-specific drug delivery vehicles. The so-called internal phase separation method is widely used to produce polymeric Janus particles because it is applicable to most polymers and amenable to scale up. In this method, when the volatile organic solvent is completely evaporated, Janus particles are formed in the aqueous system. The morphology and stability of such particles depend on various interfacial tensions. It is inconvenient and costly to screen good combinations of biocompatible/biodegradable polymers capable of producing Janus particles by measuring surface/interfacial tensions in polymeric Janus particle aqueous system. Little atomistic simulation work has been done to explore the interfacial interactions governing Janus particle formation. Interfacial tensions and binding energies of various systems were approximated using atomistic simulations to determine whether Janus particle formation is favorable under the given conditions. The simulated systems consisted of poly(lactic-co-glycolic acid) (PLGA 50:50) and poly-e-caprolactone (PCL) as the matrix polymers and SDS as surfactant. Wang et al. developed a geometry map for predicting the final morphology of polystyrene (PS)/poly(methylmetacrylate) (PMMA) composite particles prepared via internal phase separation in which the particle morphology is dependent upon the interfacial tensions of the system. Specifically, the ratio of the interfacial tension between the aqueous phase and polymer phase to the interfacial tension between the oil phase and aqueous phase normalized by the interfacial tension between the oil and polymer phases corresponds to a region on the geometry map. Inside the region for Janus particle formation, there is a range of possible architectures ranging from acorn-like to crescent moon. When applied to our PLGA/PCL system, this map accurately predicted the resulting morphology of PLGA/PCL Janus particles formed by internal phase separation in an oil-in-water emulsion template based on interfacial tensions calculated for PLGA-PCL, PLGA-water, and PCL-water with and without surfactant in the aqueous phase. Additionally, the presence of drug was explored via simulations. In some cases, the inclusion of drug affects the thermodynamics of Janus particle formation. For example, the introduction of 5% w/w griseofulvin was found to significantly alter the interfacial tensions of the system, whereas the same mass fraction of curcumin does not. Simulation results were experimentally validated. The multitude of surfactant choices and drug compounds currently available makes it impossible to experimentally test each one to find the optimal formulation. Determining the effects of different drugs and surfactants on interfacial tensions and corresponding particle morphology via atomistic modeling prior to experimentation enables rational design of Janus particles.