Engineering PLGA–Lipid Hybrid Microparticlesfor Enhanced Macrophage Uptake
2020
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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
35
References
4
Citations
NaN
KQI