The development of hybrid lipid-polymer nanoparticle architectures for the sustained-release of small hydrophilic molecules

Introduction: Polymeric nanoparticles (NPs) have been utilized as drug delivery vehicles for a variety of applications. However, achieving sustained-release of small hydrophilic agents is a primary challenge for their use in prolonged delivery applications. Objective: This study investigates how novel lipid-polymer hybrid particle architectures can be used to improve the release profile of small hydrophilic encapsulants. Here, PLGA NPs were produced via electrospraying and emulsions. Particles with a core-shell architecture were produced via coaxial electrospraying and the ability of this architecture to sustain release was examined. In addition, we combined polymeric core-shell NPs with a lipid coating to improve biocompatibility, biofunctionalization, and particle release kinetics. Methods: PLGA NPs incorporating rhodamine B (RhB) as a model small molecule hydrophilic agent, were produced using electrospraying and double emulsion techniques. The PLGA NPs were coated with a lipid layer using either gentle hydration (post-synthesis, two-step), or self-assembly through emulsion (in situ, one-step). The total loading of RhB and the release profiles were determined via fluorescence spectroscopy, while physiochemical characteristics were investigated via scanning electron microscopy. Results: Polymeric and lipid-polymer hybrid particles formed via emulsion were relatively monodisperse with diameters ranging from 100-400 nm, while particles formed via electrospraying were more polydisperse with diameters ranging from 100-1000 nm. Electrosprayed coaxial and lipid-coated NPs sustained the release of RhB and demonstrated high encapsulation efficiency (EE) (~90%). In contrast, emulsion particles had a lower EE of ~70%, with the two-step lipid-coated particles exhibiting RhB leaching and a significantly lower EE of ~25%. Conclusions: Our data suggest that the novel polymeric core-shell lipid coated NP architecture shows promise to sustain the release of small molecule hydrophilic agents, and we look forward to conducting functionality experiments with chemotherapeutic agent. Future work will also evaluate NP morphology using scanning transmission electron microscopy (STEM) and energy dispersive x-ray spectroscopy (EDS)