| Autor: |
Maghrebi S; Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of South Australia, Adelaide, South Australia 5000, Australia., Jambhrunkar M; Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of South Australia, Adelaide, South Australia 5000, Australia., Joyce P; Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of South Australia, Adelaide, South Australia 5000, Australia., Prestidge CA; Clinical and Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of South Australia, Adelaide, South Australia 5000, Australia. |
| Abstrakt: |
Strategies to improve the uptake of particulate delivery systems to macrophages are required for the advancement of therapeutic solutions to a range of disease states, including human immunodeficiency virus (HIV), tuberculosis, and cystic fibrosis. In this study, poly(lactic- co -glycolic) acid (PLGA) nanoparticles were combined with lipid nanoparticles, via the process of spray drying, to overcome the physiochemical limitations associated with the individual precursor systems. The hybrid nanoparticle-in-microparticle structure was investigated for its ability to redisperse in aqueous media and, subsequently, enhance particle uptake into RAW 267.4 macrophages. Moreover, the surface charge of PLGA-lipid hybrid (PLH) microparticles was varied by combining positively and negatively charged PLGA nanoparticles with negatively charged lipid nanoparticles, in an attempt to elucidate the impact of surface charge on intracellular internalization within macrophages. Anionic PLH particles were shown to increase the particle uptake 3.1 times more than the cationic PLH particles, which was established to be due to the ability of the negatively charged particles to redisperse in aqueous media into the precursor lipid and PLGA nanoparticles, due to repulsive electrostatic interactions, while positively charged particles remained as micron-sized agglomerates during redispersion. Importantly, the macrophage uptake of anionic PLH microparticles was 2.1- and 4.7-fold greater than the positively and negatively charged precursor PLGA nanoparticles, which highlights the superiority of the hybrid structure to induce endocytic pathways for intracellular internalization. These findings provide understanding for the uptake of particles by phagocytic cells and therefore guide the rational development of next-generation nanocarriers that aim to deliver encapsulated cargo to macrophages. |
