Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS)

Figures

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  Figure 1. Dependence of the fraction of simvastatin released from SVPLA microspheres versus time.

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  Figure 2. SV deposition in the vessel wall after administration of different concentrations of suspended SVPLA, expressed as a percentage of the total dose administered to the vessel (ia and iv). * p < 0.01 vs. control (Control; SV per os; no trace of SV in the vessel wall after p.os administration); A—aorta: V—vein. SV dispersion concentration; A: 0.3500 mg/mL.

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  Figure 3. Preparation of rat aorta. PLA-DH microspheres on the surface of the vascular wall. Scanning electron microscopy image (SEM, Jeol 5500LV, Akishima, Japan), 1000× magnification.

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  Figure 4. Preparation of rat aorta. PLA-DH microspheres immersed in the aortic wall after administration. Fluorescence microscopy image (Nikon Eclipse TE 2000-S, Japan), 100× magnification.

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  Figure 5. Preparation of rat aorta. Visible microspheres immersed in the vessel wall and a pass. Electron microscopy image (SEM, Jeol 5500LV, Akishima, Japan), 500× magnification.

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  Figure 6. The preparation of rat iliac vein. PLA-DH microspheres visible in the vessel after iv administration. Fluorescence microscopy images (Nikon Eclipse TE 2000-S, Akishima, Japan), 200× magnification.

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  Figure 7. The presence of macrophages in the wall of the aorta after 24 h (groups receiving SVPLA (B and C SVPLA) vs. SV p.os and control). SV dispersion concentration; B: 0.1750 mg/mL, C: 0.0875 mg/mL. SV orally 0.6 mg/kg; Control; saline 0.9% NaCl. Each group n = 6; six vascular samples (aorta) were tested per animal (total 36 per group).

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  Figure 8. The presence of macrophages in the vessel wall (aorta) after 7 days (groups receiving B and C SVPLA vs. p.os and control). SVPLA dispersion concentration; B: 0.1750 mg/mL, C: 0.0875 mg/mL. SV orally 0.6 mg/kg; Control; saline 0.9% NaCl. Each group n = 6; six vascular samples (aorta) were tested per animal (total 36 per group).

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  Figure 9. The presence of macrophages in the vessel wall (aorta) after 28 days (groups receiving B and C SVPLA vs. p.os and control). SV dispersion concentration; B: 0.1750 mg/mL, C: 0.0875 mg/mL. SV orally 0.6 mg/kg; Control; saline 0.9% NaCl. Each group n = 6; six vascular samples (aorta) were tested per animal (total 36 per group).

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  Figure 10. The velocity distribution of erythrocytes after administration of SVPLA microspheres vs. control. Animal model of microcirculation (mice).