Biodegradable poly(ε-caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen
Biodegradable poly(ε-caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen
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DOI：
10.1016/s0378-5173(02)00483-0
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发表时间：
2002-12-05
影响因子：
5.8
通讯作者：
Amiji, MM
中科院分区：
文献类型：
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作者：
Chawla, JS;Amiji, MM
为了增加雌激素受体（ER）阳性乳腺癌中他莫昔芬的局部浓度，我们开发并表征了聚（epsilon-己内酯）（PCL）纳米颗粒配方。采用丙酮-水体系溶剂置换法制备纳米颗粒。粒径分析、扫描电子显微镜、zeta电位测量和差示扫描量热法（DSC）用于纳米颗粒的表征。在37度的磷酸盐缓冲盐水（PBS, pH 7.4）中进行假单胞菌脂肪酶存在和不存在的生物降解研究。采用高效液相色谱法分析不同浓度下他莫昔芬的负载，确定最佳负载浓度。体外释放研究在含PBS的0.5% （w/v）十二烷基硫酸钠（SLS）中进行，温度为37℃。在MCF-7乳腺癌细胞中检测了荧光标记纳米颗粒的细胞摄取和分布。SEM显微图和Coulter分析显示，纳米颗粒呈球形，粒径分布均匀（250 ~ 300 nm）。Zeta电位分析显示，负载他莫昔芬的制剂表面带+25 mV的正电荷。PCL是疏水性结晶聚酯，单独在PBS中不能降解，但脂肪酶的存在增强了降解。他莫昔芬的最大加载效率为64%。观察到他莫昔芬最初的爆发释放，可能是由于药物在纳米颗粒表面的显著存在。MCF-7细胞通过非特异性内吞作用吸收了所给纳米颗粒剂量的大部分。1小时后，在核周区域发现了纳米颗粒。研究结果表明，选择性内质网调节剂的纳米颗粒配方，如他莫昔芬，将通过在内质网附近递送药物来提供更高的治疗效果。(C) 2002 Elsevier Science B.V.版权所有
To increase the local concentration of tamoxifen in estrogen receptor (ER) positive breast cancer, we have developed and characterized nanoparticle formulation using poly(epsilon-caprolactone) (PCL). The nanoparticles were prepared by solvent displacement method using acetone-water system. Particle size analysis, scanning electron microscopy, zeta potential measurements, and differential scanning calorimetry (DSC) were used for nanoparticle characterization. Biodegradation studies were performed in the presence and absence of Pseudomonas lipase in phosphate-buffered saline (PBS, pH 7.4) at 37 degreesC. Tamoxifen loading over different concentrations was analyzed by high-performance liquid chromatography (HPLC) and the optimum loading concentration was determined. In vitro release studies were performed in 0.5% (w/v) sodium lauryl sulfate (SLS) containing PBS at 37 degreesC. Cellular uptake and distribution of fluorescent-labeled nanoparticles was examined in MCF-7 breast cancer cells. SEM micrographs and Coulter analysis showed nanoparticles with spherical shape and uniform size distribution (250-300 nm), respectively. Zeta potential analysis revealed a positive surface charge of +25 mV on the tamoxifen-loaded formulation. Being hydrophobic crystalline polyester, PCL did not degrade in PBS alone, but the degradation was enhanced by the presence of lipase. The maximum tamoxifen loading efficiency was 64%. Initial burst release of tamoxifen was observed, probably due to significant surface presence of the drug on the nanoparticles. A large fraction of the administered nanoparticle dose was taken up by MCF-7 cells through non-specific endocytosis. The nanoparticles were found in the perinuclear region after 1 h. Results of the study suggest that nanoparticle formulations of selective ER modulators, like tamoxifen, would provide increased therapeutic benefit by delivering the drug in the vicinity of the ER. (C) 2002 Elsevier Science B.V. All rights reserved.