Physical Immobilization of Drug Nanocarriers in Uniform Hydrogel Microparticles and their Molecular Network-Mediated Release Behaviors

Abstract

Liposomes can encapsulate both hydrophilic and hydrophobic active ingredients, thus making them widely useful in fields of pharmaceuticals, cosmetics, and foods. However, its vesicular structure is readily vulnerable to amphiphilic molecules with low packing parameters. Therefore, it is critical to developing a technique to overcome this drawback. This study introduces a drop-based microfluidic approach to physically immobilize liposomes in microgel (liposome@microgel) particles. For this, we generate a uniform liposome-in-oil-in-water emulsion in a capillary-based microfluidic device. Basically, we have investigated how the flow rate and flow composition in micro-channels affect the generation of embryo emulsion drops. Then, the uniform emulsion is solidified by photo-polymerization. From the characterization of hydrogel mesh sizes, we have figured out that the liposome@microgel particles have a bigger apparent mesh size than bare microgel particles. The size difference is approximately 30 Å. This is because liposomes take space in the hydrogel mesh. In our further study on drug releasing, we have observed that the immobilization of liposomes in the microgel particles can not only remarkably retard drug releasing, but also show a sustained release behavior by 5 order of magnitude in comparison with the bare microgel particles, which stems from the enhanced viscosity of the surrounding hydrogel phase. In our continued study, we introduce a flexible and straightforward method for the immobilization of polymeric micelles in monodisperse suspensions of hydrogel microparticles. Hydrogel particles loaded with polyglycerin-b-poly(ε-caprolactone) micelles are prepared using a capillary-based microfluidic method. For this, a uniform water-in-oil emulsion is generated in a microfluidic device. The aqueous dispersion contains polymeric micelles, monomers, and photo-initiators. Then, the emulsion drops are photo-polymerized to transfer them to hydrogel particles. The hydrogel phase is made of poly (2-methacryloyloxyethyl phosphorylcholine), PMPC that has an enhanced biocompatibility due to the phosphatidyl choline moiety in the backbone. The hydrogel mesh size in presence of polymeric micelles increased by approximately 10% compared with the mesh size of bare hydrogel particles. Finally, we have demonstrated that the microfluidic approach is indeed useful for physically immobilizing polymeric micelles in between PMPC hydrogel meshes, which provides a means to regulate the release behavior of active ingredients encapsulated in the polymeric micelles.