Sustained release and enhanced oral bioavailability of rivaroxaban by PLGA nanoparticles with no food effect
Sustained release and enhanced oral bioavailability of rivaroxaban by PLGA nanoparticles with no food effect
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DOI：
10.1007/s11239-019-02022-5
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发表时间：
2020-01-02
影响因子：
4
通讯作者：
Aldayel, Abdullah M.
中科院分区：
文献类型：
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作者：
Anwer, Md Khalid;Mohammad, Muqtader;Aldayel, Abdullah M.
本研究的目的是提高利伐沙班（RXB）的生物利用度，减少食物效应。采用乳液溶剂蒸发法制备了负载RXB的PLGA纳米颗粒（RXB-PLGA- nps），并采用中心复合设计（CDD）对其进行了优化。优化后的RXB-PLGA- nps （F8）由PLGA （125 mg）、PVA （0.5%w/w）和RXB （20 mg）组成，粒径（496 +/- 8.5 nm）、PDI（0.607）、ZP （- 18.41 +/- 3.14 mV）、EE %（87.9 +/- 8.6）和DL %（9.5 +/- 1.6）。进一步对优化后的NPs （F8）进行DSC、FTIR、SEM和体外释放研究。在禁食和喂养状态大鼠身上进行了与市售片剂XARELTO (R)的比较药代动力学研究。与商业片剂（XARELTO (R)）相比，RXB-PLGA-NPs （F8）在禁食和喂养状态下均表现出显著的生物利用度提高。此外，NPs （F8）中RXB的生物利用度在食物存在下不受影响。
The purpose of the currents study was to enhance bioavailability of rivaroxaban (RXB) and reduce the food effect. RXB loaded PLGA nanoparticles (RXB-PLGA-NPs) were prepared by emulsion solvent evaporation method and optimized using central composite design (CDD). The optimized RXB-PLGA-NPs (F8) with composition, PLGA (125 mg), PVA (0.5%w/w) and RXB (20 mg) was found optimum with particle size (496 +/- 8.5 nm), PDI (0.607), ZP (- 18.41 +/- 3.14 mV), %EE (87.9 +/- 8.6) and %DL (9.5 +/- 1.6). The optimized NPs (F8) was further evaluated in vitro for DSC, FTIR, SEM and in vitro release studies. A comparative pharmacokinetic studies with commercial tablet (XARELTO (R)) were conducted on fasted and fed state rats. Compared to commercial tablet (XARELTO (R)), the RXB-PLGA-NPs (F8) exhibited a significant enhancement of bioavailability in both fasted and fed state. In addition, the bioavailability of RXB from NPs (F8) was found unaffected in the presence of food.