Influence of molecular size on the retention of polymeric nanocarrier diagnostic agents in breast ducts.

Influence of molecular size on the retention of polymeric nanocarrier diagnostic agents in breast ducts.
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DOI:
10.1007/s11095-012-0763-z
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发表时间:
2012-09
影响因子:
3.7
通讯作者:
Sinko PJ
Sinko PJ
中科院分区:
医学3区
文献类型:
--
作者:
Singh Y;Gao D;Gu Z;Li S;Rivera KA;Stein S;Love S;Sinko PJ

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采用无创光学成像方法研究纳米载体分子大小和形状对正常大鼠乳腺导管保留的影响。将不同分子量和形状(线性、双臂、四臂和八臂)的阿霉素标记的PEG纳米载体导管内给予(50 nmol)雌性Sprague-Dawley大鼠。非侵入性地获得全身图像。荧光强度(即,导管中剩余的量)相对于时间作图以估计纳米载体导管滞留半衰期(t1/2)。采集血浆样品,并评估吸收的纳米载体的药代动力学(Tmax,Cmax)。线性1/2、20、30、40和双臂60 kDa纳米载体的t1/2分别为6.7 ± 0.9、16.1 ± 4.1、16.6 ± 3.4、21.5 ± 2.7和19.5 ± 6.1 h,而四臂20、40和八臂20 kDa纳米载体的t1/2分别为9.0 ± 0.5、11.5 ± 1.9、11.5 ± 1.9、11.5 ± 1.8 h。12.6 ± 3.0 h。未结合荧光素的t1/2显著较低(14.5 ± 1.4 min)。12、40、60 kDa纳米载体的Tmax分别为1、24和32 h,荧光素的Tmax仅为30 min。由于正常乳腺导管具有高度渗透性,因此使用纳米载体可能有助于延长诊断和/或治疗剂的导管保留。
To investigate the influence of nanocarrier molecular size and shape on breast duct retention in normal rats using a non-invasive optical imaging method. Fluorescein-labeled PEG nanocarriers of different molecular weights and shapes (linear, two-arm, four-arm, and eight-arm) were intraductally administered (50 nmol) to female Sprague-Dawley rats. Whole body images were obtained non-invasively. Fluorescence intensities (i.e., amount remaining in duct) were plotted against time to estimate the nanocarrier ductal retention half-lives (t1/2). Plasma samples were taken and the pharmacokinetics (Tmax, Cmax) of absorbed nanocarriers was also assessed. The t1/2 of linear 12, 20, 30, 40, and two-arm 60 kDa nanocarriers were 6.7 ± 0.9, 16.1 ± 4.1, 16.6 ± 3.4, 21.5 ± 2.7, and 19.5 ± 6.1 h, whereas the four-arm 20, 40, and eight-arm 20 kDa had t1/2 of 9.0 ± 0.5, 11.5 ± 1.9, and 12.6 ± 3.0 h. The t1/2 of unconjugated fluorescein was significantly lower (14.5 ± 1.4 min). The Tmax for 12, 40, 60 kDa nanocarriers were 1, 24, and 32 h, respectively, and only 30 min for fluorescein. Since normal breast ducts are highly permeable, the use of nanocarriers may be helpful in prolonging ductal retention of diagnostic and/or therapeutic agents.
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影响因子: 0.9
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影响因子: 2.3
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