Emulsion-based synthesis and characterization of biphasic Janus particles for dual drug delivery

Janus particles exhibit many unique chemical, optical, electrical, and physical properties due to their two chemically distinct surfaces. They are highly sought after for diverse applications across many fields including electronics, energy, catalysis, and emulsion stabilization. Janus particles also hold great promise in the field of biomedical engineering as drug delivery vehicles, theranostic platforms, and components of biosensors. As drug delivery vehicles, they offer a platform for co-encapsulating drugs with widely disparate solubility as well as independent release kinetics. However, large-scale synthesis methods are needed before Janus particles can realize their full potential in biomedicine. A novel technique based on the phase separation of two immiscible polymers and/or lipids within single O/W and double W/O/W emulsion droplets is presented for the production of Janus particles. The effects of various formulation and process variables on final Janus particle properties including particle size, stability, morphology, and encapsulation efficiency are studied. A wide range of Janus particle morphologies were synthesized, including acorn-like, spherical, crescent moon, and two nearly separated droplets. From a purely thermodynamic perspective, particle shape is a function of the interfacial tensions between the two polymers, as well as the interfacial tensions between each of the polymers and the aqueous phase containing surfactant. These interfacial tensions are adjusted by changing the type and concentration of surfactant in the water phase, making a wide range of morphologies accessible. In order to quantifiably describe the influence of interfacial tension on particle morphology, a thermodynamic model for the prediction of Janus particle morphology was developed. The model is derived from first-principles, in which the exact shape of a Janus particle is extracted via total free energy minimization of Janus particles modeled as two overlapping semicircles. In reverse, particle geometry measurements obtained from microscopy can be applied to the model in order to explicitly calculate the volume ratio and the surface tension of each of the three interfaces. The ability to control Janus particle shape is of fundamental importance for many potential applications, as function depends on structure. Janus particles were applied to a case study involving the treatment of lung cancer with doxorubicin, a broad spectrum chemotherapeutic, and curcumin, a bioflavanoid with antioxidant, anti-inflammatory, and antitumor effects. The Janus particles containing doxorubicin and curcumin completely inhibited tumor growth over a four-week treatment period, attesting to the advantages of bicompartmental Janus carriers for dual drug delivery of synergistic compounds.Ph.D.Includes bibliographical referencesby Jennifer Sherri Winkle