Polymer-Based Dual-Responsive Self-Emulsifying Nanodroplets as Potential Carriers for Poorly Soluble Drugs

A biodegradable amphiphilic liquid polymer was designed to form self-emulsifying nanodroplets in water for delivering poorly soluble drugs. The polymer was composed of multiple short blocks of poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) connected through acid-labile acetal linkages. With an overall average molecular weight of over 18 kDa, the polymer remained as a viscous liquid under room and physiological temperatures. Dispersing the polymer in an aqueous buffer gave rise to highly stable micelle-like nanodroplets with an average size of approximately 15-20 nm. The nanodroplet dispersions underwent reversible temperature-sensitive aggregation with cloud points ranging from 45 to 50 °C, depending on polymer concentration. Nuclear magnetic resonance (NMR) and dynamic light scattering analyses revealed that while the nanodroplets were stable at pH 7.4 for several days, hydrolysis of the acetal linkages in the polymer backbone was much accelerated under mildly acidic pH 5.0, resulting in the formation of large microdroplets. Nile red (NR), a poorly water-soluble fluorophore, can be solubilized in the nanodroplets, and efficient intracellular delivery of NR was achieved. The hydrophobic indocyanine green (ICG) was also encapsulated in the nanodroplets. Near-infrared (NIR) fluorescence imaging and in vivo biocompatibility of the ICG-loaded nanodroplets were demonstrated in mice. In summary, the self-emulsifying nanodroplets of amphiphilic liquid polymer would be a promising material system for poorly soluble drug delivery and imaging in vivo.