Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods
Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods
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DOI：
10.1002/jbm.a.30914
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发表时间：
2007-04-01
影响因子：
4.9
通讯作者：
Gao, Jinming
中科院分区：
文献类型：
--
作者：
Weinberg, Brent D.;Ai, Hua;Gao, Jinming
本研究的目的是在兔模型中评价含多柔比星的聚（D，L-丙交酯-共-乙交酯）（PLGA）植入物用于肝癌瘤内治疗的抗肿瘤疗效和局部药物分布。使用65%PLGA、21.5%NaCl和13.5%多柔比星制备圆柱形聚合物毫杆（长度8 mm，直径1.5mm）。将这些植入物放置在兔的VX 2肝肿瘤（n = 16，直径类似于8 mm）的中心。在millirod植入后4天和8天移除肿瘤，并且使用肿瘤大小测量、肿瘤组织学和药物分布的荧光测量来评估抗肿瘤功效。在第4天（0.17 +/- 0.06 vs. 0.31 +/- 0.08 cm（2），P = 0.048）和第8天（0.14 +/- 0.04 vs. 1.8 +/- 0.8 cm（2），P = 0.025），治疗的肿瘤小于未治疗的对照。药物分布曲线表明，在两个时间点肿瘤核心处的阿霉素浓度较高（> 1000 μ g/g），第4天和第8天的药物渗透距离分别为2.8 mm和1.3 mm。组织学检查证实整个肿瘤组织坏死。可生物降解的聚合物millirods通过在八天的时间内向肿瘤组织提供高浓度的多柔比星而成功地治疗了原发性肿瘤块。(c)2006 Wiley Periodicals，Inc. J Biomed Mater Res 81 A：161-170，2007.
The purpose of this study was to evaluate the antitumor efficacy and local drug distribution from doxorubicin-containing poly(D,L-lactide-co-glycolide) (PLGA) implants for intratumoral treatment of liver cancer in a rabbit model. Cylindrical polymer millirods (length 8 mm, diameter 1.5 mm) were produced using 65% PLGA, 21.5% NaCl, and 13.5% doxorubicin. These implants were placed in the center of VX2 liver tumors (n = 16,similar to 8 mm in diameter) in rabbits. Tumors were removed 4 and 8 days after millirod implantation, and antitumor efficacy was assessed using tumor size measurements, tumor histology, and fluorescent measurement of drug distribution. The treated tumors were smaller than the untreated controls on both day 4 (0.17 +/- 0.06 vs. 0.31 +/- 0.08 cm(2), P = 0.048) and day 8 (0.14 +/- 0.04 vs. 1.8 +/- 0.8 cm(2), P = 0.025). Drug distribution profiles demonstrated high doxorubicin concentrations (> 1000 mu g/g) at the tumor core at both time points and drug penetration distances of 2.8 and 1.3 mm on day 4 and 8, respectively. Histological examination confirmed necrosis throughout the tumor tissue. Biodegradable polymer millirods successfully treated the primary tumor mass by providing high doxorubicin concentrations to the tumor tissue over an eight day period. (c) 2006 Wiley Periodicals, Inc. J Biomed Mater Res 81A: 161-170, 2007.