Effect of a Solid Lipid Nanoparticle Formulation on the Bioavailability of 4-(N)-Docosahexaenoyl 2', 2'-Difluorodeoxycytidine After Oral Administration.
Effect of a Solid Lipid Nanoparticle Formulation on the Bioavailability of 4-(N)-Docosahexaenoyl 2', 2'-Difluorodeoxycytidine After Oral Administration.
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DOI：
10.1208/s12249-020-1617-3
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发表时间：
2020-01-22
影响因子：
3.3
通讯作者：
Cui Z
中科院分区：
文献类型：
--
作者：
Valdes SA;Alzhrani RF;Lansakara-P DSP;Cui Z
在此之前，我们开发了具有抗肿瘤活性的化合物4-（N）-二十二碳六烯酰基2′，2′-二氟脱氧胞苷（DHA-dFdC）的固体脂质纳米粒（SLN）制剂。在此，我们研究了使用固体脂质纳米粒（即DHA-dFdC-SLN）通过口服途径施用DHA-dFdC的可行性。在模拟胃肠液中，DHA-dFdC-SLN不聚集。DHA-dFdC固体脂质纳米粒在模拟胃肠液中的释放缓慢，但在模拟肠液中的释放略快于模拟胃液。在经口给予DHA-dFdC-SLN的小鼠中，血浆DHA-dFdC浓度-时间曲线的Tmax为约1.7 h，Cmax为17.01 μg/mL。以DHA-dFdC-SLN形式给药时，DHA-dFdC的绝对口服生物利用度约为68%（基于AUC 0 -24 h值），而DHA-dFdC的相对口服生物利用度（与吐温80/乙醇水溶液中的DHA-dFdC相比）为126%。最后，与口服DHA-dFdC溶液相比，口服DHA-dFdC-SLN显著增加了预先建立的B16-F10鼠黑素瘤小鼠的存活率。得出结论，与DHA-dFdC溶液相比，固体脂质纳米颗粒制剂在口服给药后增加了DHA-dFdC的生物利用度。
Previously, we developed a solid lipid nanoparticle (SLN) formulation of 4-(N)-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC), a compound with promising antitumor activity. Herein, we studied the feasibility of administering the DHA-dFdC by the oral route using the solid lipid nanoparticles (i.e. DHA-dFdC-SLNs). In simulated gastrointestinal fluids, the DHA-dFdC-SLNs did not aggregate. The release of the DHA-dFdC from the solid lipid nanoparticles in simulated gastrointestinal fluid was slow, but was slightly faster in simulated intestinal fluid than in simulated gastric fluid. In mice orally administered with DHA-dFdC-SLNs, plasma DHA-dFdC concentration vs. time curve has a Tmax of ~1.7 h and a Cmax of 17.01 μg/mL. The absolute oral bioavailability of DHA-dFdC when given as DHA-dFdC-SLNs was ~68% (based on AUC0-24 h values), while the relative oral bioavailability DHA-dFdC (compared to DHA-dFdC in a Tween 80/ethanol-in-water solution) was 126%. Finally, in mice with pre-establish B16-F10 murine melanoma, oral DHA-dFdC-SLNs increased their survival significantly, as compared to oral administration of the DHA-dFdC solution. It is concluded that the solid lipid nanoparticle formulation increased the bioavailability of the DHA-dFdC upon oral administration, as compared to the DHA-dFdC solution.
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影响因子：
4.7
作者：
Zhu S;Lansakara-P DS;Li X;Cui Z
通讯作者：
Cui Z
口服 4-(N)-硬脂酰吉西他滨纳米颗粒抑制小鼠模型中的肿瘤生长
影响因子：
--
作者：
Wang C;Zheng Y;Sand Oval MA;Valdes SA;Chen Z;Lansakara-P DS;Du M;Shi Y;Cui Z
通讯作者：
Cui Z
影响因子：
5.8
作者：
Muller, RH;Ruhl, D;Runge, SA
通讯作者：
Runge, SA
影响因子：
3.6
作者：
Lin, Chih-Hung;Chen, Chun-Han;Lin, Zih-Chan;Fang, Jia-You
通讯作者：
Fang, Jia-You
影响因子：
10.8
作者：
Li, HouLi;Zhao, XiaoBin;Lou, HongXiang
通讯作者：
Lou, HongXiang