(674e) Biodegradable Janus Particles for Drug Delivery: Bi-Compartmental Encapsulation of Two API of Disparate Solubility

Janus particles have unique chemical, optical, electrical, and physical properties that set them apart from their isotropic counterparts. Janus particles hold great promise as tiny colloidal carriers capable of meeting the demand for highly sophisticated drug delivery systems with multiple functionalities. The biphasic nature of Janus particles allows for temporally controlled release of multiple therapeutic and diagnostic agents in a specific order and with independent release rates. Biodegradable Janus particles were synthesized from a 2.5% w/v solution of PLGA/PCL (50/50 weight ratio) or PLGA/Precirol® (75/25 weight ratio) in dichloromethane (DCM) emulsified into an aqueous solution containing 0.3% w/v PVA and 0.1% w/v sodium dodecyl benzylsulfate (SDBS). Water-insoluble drugs are dissolved in the oil phase along with the polymers and lipids, while water-soluble drugs are adsorbed onto the particle surface post-synthesis. Emulsification and homogenization can be achieved using manual shear (low energy), a rotor stator homogenizer (moderate energy), a high pressure homogenizer (high energy), or a series of these. The higher the energy applied in the emulsification step, the smaller the emulsion droplet. After emulsification and homogenization, the solvent diffuses from the oil droplets into the aqueous phase and then evaporates out from the water/air interface. Solvent removal leads to precipitation of the immiscible polymer and/or lipid components into bicompartmental Janus particles. Biocompatibility and cell uptake of both polymer-polymer and polymer-lipid Janus particles have been studied in vitro. Fluorescent PLGA/Precirol® Janus nanoparticles were internalized by A549 human lung cancer cells after a 24 hour incubation period. The PLGA component was dyed with green-fluorescing FITC, while the Precirol® tail was dyed with red-fluorescing DiR. Superimposition of the images obtained from the green and red channels showed co-localization of the PLGA and Precirol® components inside the cells, indicating that the Janus particles remained intact during cell entry. Biodistribution of the PLGA/Precirol® Janus particles after inhalation was studied in vivo with mice. Two different sizes (155 nm and 450 nm) and methods of administration (inhalation and intravenous injection) were tested. As expected, it was found that the 450 nm particles administered via inhalation overwhelmingly localized to the lungs. The 155 nm particles delivered by inhalation were presumably exhaled after inspiration due to their small size. Both the 155 nm and 450 nm particles delivered intravenously and the 155 nm particles delivered through inhalation predominantly localized in the liver with minimal deposition in the lungs. To demonstrate co-encapsulation of two drugs with widely disparate solubility, PLGA/Precirol® Janus nanoparticles containing doxorubicin and curcumin were prepared for the treatment of lung cancer. Curcumin is a hydrophobic polyphenol with antioxidant and antitumor properties, and doxorubicin is a hydrophilic chemotherapeutic. These particles encapsulated curcumin in the polymer phase and doxorubicin in the lipid phase. Therapeutic efficacy of the PLGA/Precirol® Janus nanoparticles containing curcumin and doxorubicin was also fully demonstrated in vitro using A549 human lung cancer cells.