Influence of Fatty Acid Modification on Uptake of Lovastatin-Loaded Reconstituted High Density Lipoprotein by Foam Cells

Yang, Yu-Chu; Ji, Wang; He, Hongliang; Zhang, Wenli; Zhang, Yuansheng; Liu, Jianping

doi:10.1007/s11095-018-2419-0

Cited by 3 publications

(4 citation statements)

References 48 publications

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“…The s-rHDL carrier was prepared by a film dispersion-apoA-I incubation method . Briefly, soy lecithin (200 mg), cholesterol (20 mg), cholesterol oleate (10 mg), and glycerol trioleate (10 mg) were dissolved in 15 mL of methanol/chloroform (1:1, v/v) solvent and evaporated to form a thin film with a rotary evaporator for 1 h at 40 °C.…”

Section: Methodsmentioning

confidence: 99%

“…20 In contrast, spherical rHDL (s-rHDL) possesses a solid hydrophobic core comprised of triglycerides and cholesterol ester, into which the hydrophobic drugs could be incorporated, 21 providing more space for the payload drug and being more stable in the systemic circulation. 22 Although encapsulation of LOV with the s-rHDL carrier has been attempted, 23,24 rational design of a LOV-loaded s-rHDL drug delivery system (LOV-s-rHDL) based on the medianeffect principle for the synergistic anti-atherosclerotic effect has not been explored. Besides, the safety profile of the biomimetic LOV-s-rHDL has not been evaluated.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The s-rHDL carrier was prepared by a film dispersion-apoA-I incubation method. 23 Briefly, soy lecithin (200 mg), cholesterol (20 mg), cholesterol oleate (10 mg), and glycerol trioleate (10 mg) were dissolved in 15 mL of methanol/ chloroform (1:1, v/v) solvent and evaporated to form a thin film with a rotary evaporator for 1 h at 40 °C. After further drying under a vacuum oven overnight, the thin film was hydrated with 15 mL of Tris-HCl buffer (pH 8.0) in an ultrasound bath sonicator and homogenized by an Ultra-Homogenize in an ice bath at 300 W for 10 min.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Although encapsulation of LOV with the s-rHDL carrier has been attempted, , rational design of a LOV-loaded s-rHDL drug delivery system (LOV-s-rHDL) based on the median-effect principle for the synergistic anti-atherosclerotic effect has not been explored. Besides, the safety profile of the biomimetic LOV-s-rHDL has not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Rational Design of Lovastatin-Loaded Spherical Reconstituted High Density Lipoprotein for Efficient and Safe Anti-Atherosclerotic Therapy

Jiang

Tang

et al. 2019

Mol. Pharmaceutics

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Reconstituted high density lipoprotein (rHDL) is a biomimetic nanoparticle with plaque targeting and anti-atherosclerotic efficacy. In this work, we report on a strategy to rational design of lovastatin (LOV)-loaded spherical rHDL (LOV-s-rHDL) for efficient and safe anti-atherosclerotic therapy. Briefly, three LOV-s-rHDLs were formulated with LOV/s-rHDL at ratios of 8:1, 10:1, and 15:1 upon their respective median-effect values (D m). The combined inhibitory effect between LOV and s-rHDL of different LOV-s-rHDL formulations on DiI-labeled oxLDL internalization was systemically investigated in RAW 264.7 cells based on the median-effect principle. Median-effect analysis demonstrated that the optimized LOV-s-rHDL was formulated with a ratio of 10:1 (D m LOV:D m s‑rHDL), in which LOV and s-rHDL carrier showed the best synergistic effect, presumably ascribed to their inhibitory effect on CD36 and SR-A expression according to the Western blot analysis. In vivo pharmacodynamics studies showed that the optimized LOV-s-rHDL displayed the most pronounced anti-atherosclerotic effect on decreasing plaque area and reducing the MMP level following an 8-week dosing regimen. In vivo atherosclerotic plaque targeting analysis revealed that s-rHDL had potent plaque targeting efficacy, probably owing to the interaction between apoA-I and scavenger receptor B-I. Furthermore, we observed that the optimized LOV-s-rHDL exhibited a favorable safety profile as evidenced by the results of a hemolysis assay, cell cytotoxicity study, and in vivo safety test. Collectively, the rational design of the biomimetic LOV-s-rHDL based on the median-effect analysis provides an efficient strategy to achieve a synergistic and safe anti-atherosclerotic therapy.

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Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rational Design of Lovastatin-Loaded Spherical Reconstituted High Density Lipoprotein for Efficient and Safe Anti-Atherosclerotic Therapy

Jiang

Tang

et al. 2019

Mol. Pharmaceutics

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Shuttle/sink model composed of β-cyclodextrin and simvastatin-loaded discoidal reconstituted high-density lipoprotein for enhanced cholesterol efflux and drug uptake in macrophage/foam cells

Yang

Zhou

et al. 2020

J. Mater. Chem. B

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Regulating the Size of Simvastatin-loaded Discoidal Reconstituted Highdensity Lipoprotein: Preparation, Characterization, and Investigation of Cellular Cholesterol Efflux

Huang

Gao

Zhang

et al. 2023

CDD

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Background: Reverse cholesterol transportation is an essential way for high-density lipoprotein (HDL) particles to reduce the cholesterol burden of peripheral cells. Studies have shown that the particle size plays a crucial role in the cholesterol efflux capacity of HDLs, and the reconstituted HDLs (rHDLs) possess similar function to natural ones. bjective: 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 controlled single factor. We characterized their physicochemical properties such as particle size, zeta potential, and morphology in vitro, and evaluated their capacity of cellular cholesterol efflux in foam cells. 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 didn’t compromise the cellular cholesterol efflux capacity of different-sized ST-d-rHDL. Conclusion: Compared with the larger-sized ST-d-rHDLs, the small-sized ST-d-rHDL possessed enhanced cellular cholesterol efflux capacity similar to drug-free one, the effect of particle size on cholesterol efflux wasn’t influenced by the drug loading.

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Influence of Fatty Acid Modification on Uptake of Lovastatin-Loaded Reconstituted High Density Lipoprotein by Foam Cells

Abstract: Increased unsaturation level can facilitate lipid-interchange process where the cargo in rHDL core may transfer to VLDL more easily, and then promote the endocytosis mediated by the VLDL receptor.

Cited by 3 publications

References 48 publications

Rational Design of Lovastatin-Loaded Spherical Reconstituted High Density Lipoprotein for Efficient and Safe Anti-Atherosclerotic Therapy

Rational Design of Lovastatin-Loaded Spherical Reconstituted High Density Lipoprotein for Efficient and Safe Anti-Atherosclerotic Therapy

Shuttle/sink model composed of β-cyclodextrin and simvastatin-loaded discoidal reconstituted high-density lipoprotein for enhanced cholesterol efflux and drug uptake in macrophage/foam cells

Regulating the Size of Simvastatin-loaded Discoidal Reconstituted Highdensity Lipoprotein: Preparation, Characterization, and Investigation of Cellular Cholesterol Efflux

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