Screening strategies for surface modification of lipid-polymer hybrid nanoparticles

Lipid-polymer hybrid nanoparticles are promising platforms in the field of targeted drug delivery, integrating the positive features of polymeric and lipid nanocarriers. However, the use of bulk procedures in lipid-polymer hybrid nanoparticles formulation is hindering their large-scale manufacturing. Therefore, the aim of this study is to explore the suitability of alternative formulation methods, such as microfluidics, to obtain surface-tunable nanoparticles displaying suitable characteristics. Formulations were prepared by single-step nanoprecipitation or using a micromixer chip. The nanocarriers were then surface-modified with an aptamer and an antibody, two common nanoparticle vectorization strategies, developing an optimized functionalization protocol. Both naked and surface-modified nanoparticles were characterized in terms of size, polydispersity, zeta potential and morphology. Moreover, the aptamer/antibody association efficiency was also determined. Nano-sized monodisperse nanoparticles, exhibiting a spherical core-shell structure, were obtained through both procedures. Furthermore, all the nanocarriers were successfully functionalized, showing association efficiency values above 70%. Interestingly, microfluidic-based nanoparticles displayed a smaller size and a more positive zeta potential than those prepared by single-step nanoprecipitation. Outcomes suggest both techniques led to lipid-polymer hybrid nanoparticles displaying a similar functionalization efficiency. Conversely, the microfluidic approach provided an improved control over critical parameters, as particle size or charge, constituting an interesting alternative to traditional formulation procedures.