Abstract：
Resveratrol (RSV) has powerful antioxidant activities. However, the bioavailability is still limited due to low solubility and transport issues. Nanocrystal technology has been introduced to address these issues; however, the bulky formulation of the nanocrystal process through nanosuspension faces a big challenge in terms of stability and scale-up ability. This work aimed to enhance the bioavailability of RSV through nanocrystal formulation incorporated into soluble mesoporous carriers for superior solid-state stability and feasibility. This formulation was designed and developed rationally through scientific justification in the nanocrystal formulation along with quality by design paradigm. Box-Behnken design was applied to determine the optimized formulation based on the particle size and distribution, drug loading, zeta potential, and supersaturation parameters. The nanocrystal was formed through evaporation of drug, polymer, and surfactant in the solvent incorporated into mesoporous material. The nanocrystal was evaluated by vibrational spectroscopy, thermal analyses, and SEM and TEM photographs, followed by crystallinity evaluation. The results indicated that the factors only affected the particle size variation, zeta potential, drug loading, and the time to reach the supersaturation peak level. The optimized formulation was achieved by 68 % desirability value, producing 133.3 ± 1.2 nm particle size and -24.6 mV zeta potential. The physical and chemical evaluation characterization indicated no interaction between RSV and carrier. In addition, there was no difference in crystallinity between the RSV nanocrystal and native RSV. Moreover, the RSV nanocrystal improved the bioavailability nearly twice compared to the RSV suspension.
摘要：
白藜芦醇(RSV)具有很强的抗氧化活性。然而,由于低溶解度和转运问题，生物利用度仍然有限。已经引入纳米晶体技术来解决这些问题；然而，通过纳米悬浮的纳米晶体工艺的庞大配方在稳定性和放大能力方面面临着巨大的挑战。这项工作旨在通过将纳米晶体制剂掺入可溶性介孔载体中以获得优异的固态稳定性和可行性来提高RSV的生物利用度。通过纳米晶体配方的科学论证以及设计范式的质量，合理地设计和开发了该配方。Box-Behnken设计用于根据粒度和分布确定优化配方，药物装载，zeta电位,和过饱和参数。纳米晶体是通过药物蒸发形成的，聚合物，和溶剂中的表面活性剂掺入到介孔材料中。通过振动光谱对纳米晶体进行了评估，热分析，以及SEM和TEM照片，然后进行结晶度评估。结果表明，这些因素仅影响颗粒尺寸的变化，zeta电位,药物装载，以及达到过饱和峰值水平的时间。优化的配方实现了68%的期望值，产生133.3±1.2nm粒径和-24.6mVzeta电位。物理和化学评估表征表明RSV与载体之间没有相互作用。此外,RSV纳米晶体和天然RSV之间的结晶度没有差异。此外，与RSV悬浮液相比,RSV纳米晶体将生物利用度提高了近两倍。
