The aim of the present work is to synthesize, characterize, and test self-assembled anisotropic or Janus particles designed to load anticancer drugs for lung cancer treatment by inhalation. The particles were synthesized using binary mixtures of biodegradable and biocompatible materials. The particles did not demonstrate cyto- and genotoxic effects. Janus particles were internalized by cancer cells and accumulated both in the cytoplasm and nuclei. After inhalation delivery, nanoparticles accumulated preferentially in the lungs of mice and retained there for at least 24 h. Two drugs or other biologically active components with substantially different aqueous solubility can be simultaneously loaded in two-phases (polymer-lipid) of these nanoparticles. In the present proof-of-concept investigation, the particles were loaded with two anticancer drugs: doxorubicin and curcumin as model anticancer drugs with relatively high and low aqueous solubility, respectively. However, there are no obstacles for loading any hydrophobic or hydrophilic chemical agents. Nanoparticles with dual load were used for their local inhalation delivery directly to the lungs of mice with orthotopic model of human lung cancer. In vivo experiments showed that the selected nanoparticles with two anticancer drugs with different mechanisms of action prevented progression of lung tumors. It should be stressed that anticancer effects of the combined treatment with two anticancer drugs loaded in the same nanoparticle significantly exceeded the effect of either drug loaded in similar nanoparticles alone.

In recent years, production and characterization of anisotropic particles has become of interest in a wide range of scientific fields including polymer chemistry, drug delivery, electronics, energy, and nanotechnology. In this work, we demonstrate a novel formulation for production of anisotropic particles via an internal phase separation of biodegradable components. Specifically, binary mixtures of biodegradable polymers poly(lactic-co-glycolic acid), polycaprolactone, and biodegradable lipid Precirol (glyceryl palmitostearate) were dissolved in dichloromethane, emulsified, and prepared into anisotropic particles using a modified solvent evaporation technique. During the slow evaporation process the components self-assembled into anisotropic particles with distinct morphologies. Polymer/polymer formulations resulted in compartmentalized anisotropic heterodimer particles, while polymer/lipid combinations yielded "ice cream cone" shaped particles. It was found that addition of certain active pharmaceuticals resulted in an altered, pox-like segregation at the particle surface of polymer/polymer formulations. The anisotropic nature of the particles was subsequently characterized using optical microscopy, scanning electron microscopy, zeta potential, electrophoresis, and X-ray diffraction. Successful formulations presented here may potentially be employed as multicompartmental drug carriers with staggered drug release rates or alternatively as a colloidal excipient for an arsenal of pharmaceutical applications.

Bicompartmental Janus particles have many advantages in drug delivery, including co-delivery of two compounds with varying solubilities, differential release kinetics, and two surfaces available for targeting ligands. We present a novel strategy using the double emulsion method for the coencapsulation and staggered release of a hydrophobic and hydrophilic drug from anisotropic PLGA/PCL Janus particles, as well as a UV detection method to measure the release of two different compounds from Janus particles. Curcumin and quercetin were chosen as the model hydrophobic compounds for drug loading studies, while acetaminophen (APAP) and naproxen were chosen as the model hydrophilic–hydrophobic drug pair for encapsulation methods and drug loading. Also, a similar double emulsion method was also applied for PLGA/Preicrol® Janus particles containing Doxorubicin and Curcumin. Hydrophobic drugs were encapsulated by the single O/W emulsion technique. Hydrophilic compounds required special modifications due to their poor oil solubility and tendency to escape to the outer aqueous phase during the emulsification and solvent evaporation steps. In total, three different strategies for incorporating hydrophilic drugs were employed: (1) O/W emulsion with partially water miscible solvent, (2) O/W emulsion with co-solvent (i.e. acetone, methanol, ethanol), or (3) W/O/W double emulsion. The encapsulation efficiencies and drug loading percentages were measured using UV/Vis spectroscopy and compared for the different synthesis methods. It was found that the double emulsion method resulted in the highest encapsulation efficiency and drug loading of the hydrophilic drug.

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