Controlled release of NFkappaB decoy oligonucleotides from biodegradable polymer microparticles.
Controlled release of NFkappaB decoy oligonucleotides from biodegradable polymer microparticles.
复制标题
从可生物降解的聚合物微粒中控制释放 NFkappaB 诱饵寡核苷酸。
DOI：
10.1016/s0142-9612(01)00409-4
复制
发表时间：
2002
期刊：
影响因子：
14
通讯作者：
Yaszemski,MichaelJ
中科院分区：
文献类型：
--
作者：
Zhu,Xun;Lu,Lichun;Currier,BradfordL;Windebank,AnthonyJ;Yaszemski,MichaelJ
本研究的目的是评价一种用于核因子-kappaB(核因子κB)诱骗硫代寡核苷酸(ODN)的聚乳酸/聚乙二醇(PLGA/PEGO)递送系统。制备了负载ODN的PLGA/PEG微粒子，包封率高达70%。研究了聚乙二醇用量(0、5和10wt%)、负载量(0.4、4和40μg/mg)和培养介质的pH值(pH 5、7.4和10)对聚乙二醇聚乙二醇微球体外释药动力学的影响。在pH为7.4的磷酸盐缓冲盐水(PBS)中的释药曲线在最初的2天内呈爆发式，至第18天为线性释药阶段，其余时间为最终释药阶段。无论ODN的负载密度和聚乙二醇含量如何，在pH 7.4PBS中28天后，高达85%的ODN被释放。较高的ODN负载密度会导致较低的包封率和较大的初始突发效应。聚乙二醇用量和ODN负载密度对PLGA的整体降解没有显著影响，但在酸性缓冲液pH条件下对PLGA的降解有显著的促进作用。在酸性和碱性条件下，微粒的聚集导致释放的ODN累积质量显著低于中性pH条件下释放的ODN。通过在PLGA微球中引入聚乙二醇缩乙二醇酯，降低了pH的影响。由于PLGA降解产物是酸性的，因此PLGA/PEG微粒子可能比PLGA微粒子提供更好的ODN载体。这些结果表明，PLGA/PEG微粒子可作为ODN控释的载体，值得在细胞培养和胶质母细胞瘤动物模型中进一步研究。
The objective of this study was to evaluate a poly(dl-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) delivery system for nuclear factor-kappa B (NFκB) decoy phosphorothioated oligonucleotides (ODNs). PLGA/PEG microparticles loaded with ODNs were fabricated with entrapment efficiencies up to 70%. The effects of PEG contents (0, 5, and 10wt%), ODN loading densities (0.4, 4, and 40μg/mg), and pH of the incubation medium (pH 5, 7.4, and 10) on ODN release kinetics from the PLGA/PEG microparticles were investigated in vitro for up to 28 days. The release profiles in pH 7.4 phosphate buffered saline (PBS) were characterized by an initial burst during the first 2 days, a linear release phase until day 18, and a final release phase for the rest of the period. Up to 85% of the ODNs were released after 28 days in pH 7.4 PBS regardless of the ODN loading density and PEG content. Higher ODN loading densities resulted in lower entrapment efficiencies and greater initial burst effects. The bulk degradation of PLGA was not significantly affected by the PEG content and ODN loading density, but significantly accelerated at acidic buffer pH. Under acidic and basic conditions, the aggregation of microparticles resulted in significantly lower cumulative mass of released ODNs than that released at neutral pH. The effects of pH were reduced by the incorporation of PEG into PLGA microparticles. Since the PLGA degradation products are acidic, PLGA/PEG microparticles might provide a better ODN delivery vehicle than PLGA microparticles. These results suggest that PLGA/PEG microparticles are useful as delivery vehicles for controlled release of ODNs and merit further investigation in cell culture and animal models of glioblastoma.
登录
查看更多内容
影响因子：
11.2
作者：
G. Reifenberger;Lu Liu;K. Ichimura;Schmidt Ee;V. Collins
通讯作者：
G. Reifenberger;Lu Liu;K. Ichimura;Schmidt Ee;V. Collins
影响因子：
11.2
作者：
B. Rasheed;R. McLendon;J. Herndon;H. Friedman;A. Friedman;D. Bigner;S. Bigner
通讯作者：
B. Rasheed;R. McLendon;J. Herndon;H. Friedman;A. Friedman;D. Bigner;S. Bigner
影响因子：
11.2
作者：
D. Wechsler;C. Shelly;Christy A. Petroff;C. Dang
通讯作者：
D. Wechsler;C. Shelly;Christy A. Petroff;C. Dang
合成 DNA 的纯化。
影响因子：
--
作者：
T. Brown;D. J. Brown
通讯作者：
D. J. Brown
影响因子：
14
作者：
Lu, L;Peter, SJ;Mikos, AG
通讯作者：
Mikos, AG