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Results: 5

1.
Figure 1

Figure 1. From: Lesion Complexity Determines Arterial Drug Distribution After Local Drug Delivery.

The partition coefficients (n=3) of everolimus (10 µM, blue), paclitaxel (10 nM, red) and sirolimus (10 µM, green) decrease with increasing cholesterol content (defined as the sum of free and esterified cholesterol, n=3). These data were obtained from a single 3mm thick human aorta sample that was separated into its three tunica layers. Each layer was then cut into 12 square segments (4mm×4mm); 3 for cholesterol quantification and 9 for drug quantification.

Abraham R. Tzafriri, et al. J Control Release. ;142(3):332-338.
2.
Figure 4

Figure 4. From: Lesion Complexity Determines Arterial Drug Distribution After Local Drug Delivery.

Local paclitaxel deposition scales inversely with lipid content in control (injury+normal diet, n=2) and diseased arteries (injury + cholesterol/oil diet+normal diet, n=2). Fluorescent paclitaxel (green) and lipid (inset, red) distribution in control artery (a) and in lesions of varying complexity (b)–(d). All samples imaged at the same intensity level and processed to eliminate backgrounds and artifacts with minimal residual autofluorescence exhibited by control arteries that were incubated in PBS (supplemental figure S2).

Abraham R. Tzafriri, et al. J Control Release. ;142(3):332-338.
3.

Figure 2. From: Lesion Complexity Determines Arterial Drug Distribution After Local Drug Delivery.

Drug absorption and transmural distribution in atheromatous rabbit aortae. (A) The kinetics of net arterial partitioning for control (injured + normal diet, n=3) and atheromatous (injured + cholesterol/oil diet, n=3) samples are independent of tissue state and statistically indistinguishable for paclitaxel (blue), everolimus (red) and sirolimus (green). A second subset of equilibrium incubated arteries was cryosectioned and the partition coefficient evaluated in 0.020 mm sections (n=3), from the luminal to the adventitial side. Disease state altered the distribution profile of paclitaxel (B) but not of everolimus (C).

Abraham R. Tzafriri, et al. J Control Release. ;142(3):332-338.
4.
Figure 3

Figure 3. From: Lesion Complexity Determines Arterial Drug Distribution After Local Drug Delivery.

Arterial ultrastructure determines drug distribution. Control or atherosclerotic arteries were incubated for 24h in fluorescent drug, serial sectioned and either analyzed for compositional distribution or imaged en face using a fluorescent microscope to determine drug distribution. (a,e) oil-red-O stain for lipid. (b,f) tubulin immunostain in brown; (c,g) VerHoeff stain shows elastin as black wavy lines; (d,h) fluorescent paclitaxel deposition (green). Diet and injury decreased total elastin and tubulin levels by 40±5% and 37±5%, respectively. Concomitantly, total fluorescent paclitaxel deposition dropped 73±9% and total lipid levels increased by 28±7%.

Abraham R. Tzafriri, et al. J Control Release. ;142(3):332-338.
5.
Figure 5

Figure 5. From: Lesion Complexity Determines Arterial Drug Distribution After Local Drug Delivery.

(Top) Images of neointima with fluorescent paclitaxel deposition in green (left) and Oil-Red-O stain for lipid in red (right) were processed to eliminate backgrounds and artifacts. Pixel luminosities relative to threshold values were extracted for all zones of interest, and their percentage taken as a measure of drug and lipid contents. (Bottom) Analysis of multiple sectors converged to an inverse linear correlation (R2=0.842) between drug content and lipid content per section, the more lipid in the section the less drug. Circumferential irregularities in tissue fluorescence (top) arise from unavoidable variations in tissue processing and account for the spread in fluorescent intensity that arises from tissue regions that express at high levels of lipid.

Abraham R. Tzafriri, et al. J Control Release. ;142(3):332-338.

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