Polymeric nanoparticles for increased oral bioavailability and rapid absorption using celecoxib as a model of a low-solubility, high-permeability drug.
Polymeric nanoparticles for increased oral bioavailability and rapid absorption using celecoxib as a model of a low-solubility, high-permeability drug.
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DOI：
10.1007/s11095-011-0558-7
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发表时间：
2012-02
影响因子：
3.7
通讯作者：
Shamblin, Sheri
中科院分区：
文献类型：
--
作者：
Morgen, Michael;Bloom, Corey;Beyerinck, Ron;Bello, Akintunde;Song, Wei;Wilkinson, Karen;Steenwyk, Rick;Shamblin, Sheri
证明药物/聚合物纳米颗粒可以增加低溶解度、高渗透性药物的口服吸收速率和程度。使用乙基纤维素和酪蛋白酸钠或胆汁盐制备含有塞来昔布的无定形药物/聚合物纳米颗粒。纳米粒子的特征在于使用动态光散射，透射和扫描电子显微镜，差示扫描量热法。使用高效液相色谱法进行药物释放和再悬浮研究。在犬和人中进行了药代动力学研究。一个物理模型，描述了纳米粒子的物质状态和释放性能。与市售胶囊相比，在水性混悬液中口服给药的纳米颗粒提供了更高的全身暴露量和更快的达到峰值血浆浓度，纳米颗粒在人体中达到最大药物浓度的中位时间（Tmax）为0.75 h，而市售胶囊为3 h。纳米颗粒释放塞来昔布迅速，并提供更高的溶解药物浓度比微粉化的结晶药物。纳米颗粒悬浮液可稳定数天，并可喷雾干燥以形成再悬浮于水中的干粉。药物/聚合物纳米颗粒非常适合于提供BCS II类药物的快速口服吸收和增加的生物利用度。
To demonstrate drug/polymer nanoparticles can increase the rate and extent of oral absorption of a low-solubility, high-permeability drug. Amorphous drug/polymer nanoparticles containing celecoxib were prepared using ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were characterized using dynamic light scattering, transmission and scanning electron microscopy, and differential scanning calorimetry. Drug release and resuspension studies were performed using high-performance liquid chromatography. Pharmacokinetic studies were performed in dogs and humans. A physical model is presented describing the nanoparticle state of matter and release performance. Nanoparticles dosed orally in aqueous suspensions provided higher systemic exposure and faster attainment of peak plasma concentrations than commercial capsules, with median time to maximum drug concentration (Tmax) of 0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles released celecoxib rapidly and provided higher dissolved-drug concentrations than micronized crystalline drug. Nanoparticle suspensions are stable for several days and can be spray-dried to form dry powders that resuspend in water. Drug/polymer nanoparticles are well suited for providing rapid oral absorption and increased bioavailability of BCS Class II drugs.
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影响因子：
3.8
作者：
CONNORS, KA
通讯作者：
CONNORS, KA
影响因子：
3.7
作者：
Hancock, BC;Parks, M
通讯作者：
Parks, M
影响因子：
8.4
作者：
van Wijngaarden, Jens;van Beek, Ermond;Lowik, Clemens W. G. M.
通讯作者：
Lowik, Clemens W. G. M.
影响因子：
3.3
作者：
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通讯作者：
Nasr, Mohamed
影响因子：
16.1
作者：
Porter, Christopher J. H.;Pouton, Colin W.;Charman, William N.
通讯作者：
Charman, William N.