Ding Pinggang, Chen Yuxuan, Cao Guangshang, Shen Hongxue, Ju Jianming, Li Weiguang
Department of Pharmaceutical Analysis and Metabolomics, Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China.
Drug Des Devel Ther. 2019 Jun 7;13:1947-1956. doi: 10.2147/DDDT.S201453. eCollection 2019.
We aimed to prepare two oral drug delivery systems consisting of polyoxyl 15 hydroxystearate (HS15) with pluronicF127 (F127) and HS15 with pluronicL61 (L61) to overcome the challenges of genistein's poor oral bioavailability. This provides a good strategy for enhancing the potential value of genistein. We designed two binary mixed micelle systems employing the organic solvent evaporation method using surfactants (HS15, L61, and F127). Formulations (GEN-F and GEN-L) were characterized by transmission electron microscopy. Drug content analysis, including entrapment efficiency (EE%), drug loading (DL%), and the cumulative amount of genistein released from the micelles, was performed using HPLC. The permeability of optimum formulation was measured in Caco-2 cell monolayers, and the oral bioavailability was evaluated in SD rats. The solutions of GEN-F and GEN-L were observed to be transparent and colorless. GEN-F had a lower EE% of 80.79±0.55% and a DL% of 1.69±0.24% compared to GEN-L, which had an EE% 83.40±1.36% and a DL% 2.26±0.18%. TEM results showed that the morphology of GEN-F and GEN-L was homogeneous and resembled a spherical shape. The dilution and storage conditions had no significant effect on particle size and EE%. Genistein demonstrated a sustained release behavior when encapsulated in micelles. Pharmacokinetics study showed that the relative oral bioavailability of GEN-F and GEN-L increased by 2.23 and 3.46 fold while also enhancing the permeability of genistein across a Caco-2 cell monolayer compared to that of raw genistein. GEN-F and GEN-L as a drug delivery system provide an effective strategy for enhancing and further realizing the potential value of GEN.
我们旨在制备两种口服给药系统，一种由聚氧乙烯15羟基硬脂酸酯（HS15）与普朗尼克F127（F127）组成，另一种由HS15与普朗尼克L61（L61）组成，以克服染料木黄酮口服生物利用度差的问题。这为提高染料木黄酮的潜在价值提供了一个良好的策略。我们使用表面活性剂（HS15、L61和F127）通过有机溶剂蒸发法设计了两种二元混合胶束系统。通过透射电子显微镜对制剂（GEN-F和GEN-L）进行了表征。使用高效液相色谱法进行药物含量分析，包括包封率（EE%）、载药量（DL%）以及从胶束中释放的染料木黄酮的累积量。在Caco-2细胞单层中测定最佳制剂的渗透率，并在SD大鼠中评估口服生物利用度。观察到GEN-F和GEN-L溶液是透明无色的。与GEN-L相比，GEN-F的包封率较低，为80.79±0.55%，载药量为1.69±0.24%，而GEN-L的包封率为83.40±1.36%，载药量为2.26±0.18%。透射电子显微镜结果表明，GEN-F和GEN-L的形态均匀，呈球形。稀释和储存条件对粒径和包封率没有显著影响。染料木黄酮包裹在胶束中时表现出缓释行为。药代动力学研究表明，与未加工的染料木黄酮相比，GEN-F和GEN-L的相对口服生物利用度分别提高了2.23倍和3.46倍，同时也提高了染料木黄酮在Caco-2细胞单层中的渗透率。GEN-F和GEN-L作为药物递送系统为增强并进一步实现GEN的潜在价值提供了一种有效的策略。
