Affiliation:
1. Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China
Abstract
Background:
Reverse cholesterol transportation is essential for high-density lipoprotein
(HDL) particles to reduce the cholesterol burden of peripheral cells. Studies have shown that particle
size plays a crucial role in the cholesterol efflux capacity of HDLs, and the reconstituted HDLs
(rHDLs) possess a similar function to natural ones.
Ojective:
The study aimed to investigate the effect of particle size on the cholesterol efflux capacity of
discoidal rHDLs and whether drug loadings may have an influence on this effect.
Methods:
Different-sized simvastatin-loaded discoidal rHDLs (ST-d-rHDLs) resembling nascent HDL
were prepared by optimizing key factors related to the sodium cholate of film dispersion-sodium cholate
dialysis method with a single controlling factor. Their physicochemical properties, such as particle
size, zeta potential, and morphology in vitro, were characterized, and their capacity of cellular cholesterol
efflux in foam cells was evaluated.
Results:
We successfully constructed discoidal ST-d-rHDLs with different sizes (13.4 ± 1.4 nm, 36.6 ±
2.6 nm, and 68.6 ± 3.8 nm) with over 80% of encapsulation efficiency and sustained drug release.
Among them, the small-sized ST-d-rHDL showed the strongest cholesterol efflux capacity and inhibitory
effect on intracellular lipid deposition in foam cells. In addition, the results showed that the loaded
drug did not compromise the cellular cholesterol efflux capacity of different-sized ST-d-rHDL.
Conclusion:
Compared to the larger-sized ST-d-rHDLs, the small-sized ST-d-rHDL possessed enhanced
cellular cholesterol efflux capacity similar to drug-free one, and the effect of particle size on
cholesterol efflux was not influenced by the drug loading.
Funder
National Natural Science Foundation of China
National Science and Technology Major Project of China
Publisher
Bentham Science Publishers Ltd.