Self-Assembled Bioactive Colloidal Gels as Injectable Multiparticle Shedding Platforms

abstract

Self-assembled colloidal gels are highly versatile 3D nanocluster platforms with potential to overcome the rapid clearing issues associated with standard free nanotherapeutics administration. However, the development of nanoassembled colloidal gels exhibiting autonomous multiparticle release from the bulk particle network remains elusive. Herein, we generated multiparticle colloidal gels from two nanosized building blocks: cationic poly(Dplactide-co-glycolide)-polyethylenimine (PLGA-PEI) nanoparticles and anionic zein-hyaluronan (HA) nanogels that assemble into macrosized 3D constructs via attractive electrostatic forces. The resulting colloidal gels exhibited high stability in complex culture medium as well as fitto-shape moldable properties and injectability. Moreover, nanoassembled colloidal gels encapsulated bioactive quercetin flavonoids with high loading efficacy and presented remarkable antiinflammatory activities, reducing key proinflammatory biomarkers in inflammation-activated macrophages. More importantly, because of their rationally selected building blocks zein-HA/PLGA-PEI, self-assembled colloidal platforms displayed autonomous multiparticle shedding. Both positive and negative particles released from the colloidal system were efficiently internalized by macrophages along time as evidenced by quantitative particle uptake analysis. Overall, the generated nanostructured gels represent an implantable versatile platform for focalized multiparticle delivery. In addition, the possibility to combine a higher number of particle species with different properties or stimuli-responsiveness enables the manufacturing of combinatorial nanostructured gels for numerous biomedical applications.

keywords

DRUG-DELIVERY SYSTEMS; HYDROGEL

subject category

Science & Technology - Other Topics; Materials Science

authors

Freitas, B; Lavrador, P; Almeida, RJ; Gaspar, VM; Mano, JF

our authors

acknowledgements

This work was also supported by the Programa Operacional Competitividade e Internacionalizacao (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the projects Margel (PTDC/BTM-MAT/31498/2017) and PANGEIA (PTDC/BTMSAL/30503/2017). The PANGEIA project is also acknowledged for the junior researcher contract of V.M.G. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES. P.L. acknowledges an individual PhD fellowship from the Portuguese Foundation for Science and Technology (SFRH/BD/141834/2018). Confocal images acquisition was performed in the Light imaging Microscopy (LiM) facility of iBiMED, a node of PPBI (Portuguese Platform of BioImaging) with grant agreement POCI-01-0145-FEDER-022122.

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