增强鞣花单宁,鹤草酚的生物利用度:制剂、表征和体内评价。

Enhancing the Bioavailability of the Ellagitannin, Geraniin: Formulation, Characterization, and in vivo Evaluation.

机构信息

School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia.

RVS College of Pharmaceutical Sciences, Sulur, Coimbatore, 641402, India.

出版信息

Int J Pharm. 2024 Jul 20;660:124333. doi: 10.1016/j.ijpharm.2024.124333. Epub 2024 Jun 10.

Abstract

Geraniin (GE), an ellagitannin (ET) renowned for its promising health advantages, faces challenges in its practical applications due to its limited bioavailability. This innovative and novel formulation of GE and soy-phosphatidylcholine (GE-PL) complex has the potential to increase oral bioavailability, exhibiting high entrapment efficiency of 100.2 ± 0.8 %, and complexation efficiency of 94.6 ± 1.1 %. The small particle size (1.04 ± 0.11 μm), low polydispersity index (0.26 ± 0.02), and adequate zeta potential (-26.1 ± 0.12 mV), indicate its uniformity and stability. Moreover, the formulation also demonstrates improved lipophilicity, reduced aqueous and buffer solubilities, and better partition coefficient. It has been validated by various analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. Oral bioavailability and pharmacokinetics of free GE and GE-PL complex investigated in rabbits demonstrated enhanced plasma concentration of ellagic acid (EA) compared to free GE. Significantly, GE, whether in its free form or as part of the GE-PL complex, was not found in the circulatory system. However, EA levels were observed at 0.5 h after administration, displaying two distinct peaks at 2 ± 0.03 h (T1) and 24 ± 0.06 h (T2). These peaks corresponded to peak plasma concentrations (C1 and C2) of 588.82 ng/mL and 711.13 ng/mL respectively, signifying substantial 11-fold and 5-fold enhancements when compared to free GE. Additionally, it showed an increased area under the curve (AUC), the elimination half-life (t, el) and the elimination rate constant (K). The formulation of the GE-PL complex prolonged the presence of EA in the bloodstream and improved its absorption, ultimately leading to a higher oral bioavailability. In summary, the study highlights the significance of the GE-PL complex in overcoming the bioavailability limitations of GE, paving the way for enhanced therapeutic outcomes and potential applications in drug delivery and healthcare.

摘要

姜黄素(GE)是一种著名的鞣花单宁(ET),具有广阔的应用前景,但由于其生物利用度有限,实际应用面临挑战。本研究创新性地制备了 GE 和大豆卵磷脂(GE-PL)复合物,结果显示该复合物的口服生物利用度显著提高,包封率高达 100.2±0.8%,络合率为 94.6±1.1%。同时,该复合物粒径小(1.04±0.11μm)、多分散指数低(0.26±0.02)、Zeta 电位适中(-26.1±0.12mV),表明其粒径均一、稳定性良好。此外,该复合物还表现出较强的亲脂性、较低的水相和缓冲相溶解度以及更好的分配系数。傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)和 X 射线衍射(XRD)等分析技术验证了其结构。GE 和 GE-PL 复合物在兔体内的口服生物利用度和药代动力学研究表明,与游离 GE 相比,复合物可显著提高原形药鞣花酸(EA)的血浆浓度。更为重要的是,GE 无论是游离形式还是作为 GE-PL 复合物的一部分,均未在循环系统中检出,但给药 0.5h 后即可检测到 EA,2±0.03h(T1)和 24±0.06h(T2)时出现两个明显的峰,表明与游离 GE 相比,其具有 11 倍和 5 倍的显著提升。此外,该复合物还表现出更高的曲线下面积(AUC)、更长的消除半衰期(t,el)和消除速率常数(K)。GE-PL 复合物的形成延长了 EA 在血液中的存在时间,提高了其吸收度,从而使口服生物利用度得到显著提高。综上所述,本研究突出了 GE-PL 复合物在克服 GE 生物利用度限制方面的重要性,为提高治疗效果和在药物传递和医疗保健方面的潜在应用铺平了道路。

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