Enhanced oral bioavailability of a cancer preventive agent (SR13668) by employing polymeric nanoparticles with high drug loading.
Enhanced oral bioavailability of a cancer preventive agent (SR13668) by employing polymeric nanoparticles with high drug loading.
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通过采用高载药量的聚合物纳米粒子，增强癌症预防剂 (SR13668) 的口服生物利用度。
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Y. Liu
中科院分区：
文献类型：
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作者：
Hao Shen;A. Banerjee;Paulina Mlynarska;Mathew Hautman;Seungpyo Hong;I. Kapetanovic;A. Lyubimov;Y. Liu
SR13668[2，10-Dicarbethoxy-6-methoxy-5，7-dihydro-indolo-(2，3-b)carbazole]已被证明在癌症预防中有效，但其有限的生物利用度阻碍了其临床推广。在这项研究中，我们基于对纳米沉淀和喷雾干燥竞争动力学的理解，开发了一种连续的、可扩展的过程来形成稳定的聚乳酸-乙醇酸共聚纳米颗粒包裹SR13668。优化后的处方载药量高(33.3wt%)，粒径分布窄，粒径小(150 Nm)。通过闪蒸纳米沉淀法制备的纳米颗粒悬浮液被喷雾干燥，以实现长期稳定，并在使用前方便地调整纳米颗粒的浓度。为了克服SR13668低水溶性的限制，在有机相和水相分离的溶液中测定了SR13668纳米悬浮液的体外释放。与Labrasol®配方相比，使用聚合物纳米粒的SR13668在小鼠模型中的口服生物利用度更高。
SR13668 [2,10-Dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3-b)carbazole] has been proven effective in cancer prevention, but the limited bioavailability has hindered its clinical translation. In this study, we have developed a continuous, scalable process to form stable poly(lactic-co-glycolic acid) nanoparticles encapsulating SR13668, based on understanding of the competitive kinetics of nanoprecipitation and spray drying. The optimized formulation achieved high drug loading (33.3 wt %) and small particles (150 nm) with narrow size distribution. The prepared nanoparticle suspensions through flash nanoprecipitation were spray dried to achieve long-term stability and to conveniently adjust the nanoparticle concentration before use. In vitro release of SR13668 from the nanosuspensions was measured in a solution with separated organic and aqueous phases to overcome the limit of SR13668 low water solubility. Higher oral bioavailability of SR13668 by employing polymeric nanoparticles compared with the Labrasol® formulation was demonstrated in a mouse model.