Research Center for Differentiation and Development of TCM Basic Theory, Jiangxi University of Traditional Chinese Medicine, Jiangxi Nanchang 330004, China.
National Engineering Research Center for Modernization of Traditional Chinese Medicine - Hakka Medical Resources Branch, College of Pharmacy, Gannan Medical University, Jiangxi Ganzhou, 341000, China.
Curr Drug Deliv. 2021;18(4):487-499. doi: 10.2174/1567201817666200731164902.
Essential oils are poor aqueous solubility and high volatility compounds. The encapsulation of essential oils with Cyclodextrins (CDs) can protect them from adverse environmental conditions and improve their stability. Therefore, increasing the functional capabilities of essential oils when they were used as additives in pharmaceutical and food systems. Additionally, the release of active compounds is an important issue. However, there were few studies about the effect of different CDs on the release of drugs after encapsulation. Therefore, the information on the study of release models is considerably limited.
This study aimed to (i) characterize the physico-chemical properties and release behavior of myrcene encapsulated in the four different shell matrices of α-CD, β-CD, γ-CD and 2-hydroxypropyl-β- cyclodextrin (HP-β-CD), which were selected from the perspective of stability, and (ii) determine the release mechanism of myrcene in Inclusion Complexes (ICs).
ICs of myrcene and four CDs were prepared by freeze-drying. The physico-chemical properties of ICs were fully characterized by laser diffraction particle size analyzer, Scanning Electron Microscope (SEM), Fourier-Transform Infrared spectroscopy (FT-IR) and Differential Scanning Calorimeter (DSC). The release behaviors of ICs at 50, 60, 70 and 80 °C were determined and described by zeroorder or first-order kinetics with the Henderson-Pabis, Peppas, Avrami and Page mathematical models. Moreover, the possible binding modes of ICs were identified with molecular modelling technique.
Firstly, the structure of Particle Size Distribution (PSD), FT-IR, DSC and SEM showed that (i) CDs could effectively encapsulate the myrcene molecules, and (ii) the release kinetics were well simulated by Avrami and Page models. Secondly, the release rates of the ICs experienced an unsteady state in the early stage, and gradually became almost constants period after 20 hours. Except that the release of myrcene in γ-CD/myrcene belonged to the first-order kinetic, the release models of the remaining three ICs belonged to diffusion mode. Thirdly, the calculated binding energies of the optimized structures for α-CD/myrcene, β-CD/myrcene, γ-CD/myrcene, and HP-β-CD/myrcene ICs were -4.28, -3.82, -4.04, and -3.72 kcal/mol, respectively. Finally, the encapsulation of myrcene with α-CD and β-CD was preferable according to the stability and release characteristics.
The encapsulation of myrcene was profoundly affected by the type of CDs, and the stability could be improved by complexation with suitable CDs. The binding behavior between guest and CD molecules, and the release profile of the guest molecules could be effectively explained by the kinetics parameters and molecular modelling. This study can provide an effective basis and guide for screening suitable shell matrices.
精油是水溶性差、挥发性高的化合物。环糊精（CDs）包封精油可以保护它们免受不利环境条件的影响，并提高其稳定性。因此，增加精油在药物和食品系统中作为添加剂的功能能力。此外，活性化合物的释放是一个重要问题。然而，关于不同 CDs 对包封后药物释放影响的研究很少。因此，关于释放模型的信息相当有限。
本研究旨在：（i）从稳定性的角度选择 α-CD、β-CD、γ-CD 和 2-羟丙基-β-环糊精（HP-β-CD）四种不同壳基质包封的苎烯的物理化学性质和释放行为进行表征；（ii）确定包合物中苎烯的释放机制。
通过冷冻干燥法制备苎烯与四种 CDs 的包合物。用激光衍射粒度分析仪、扫描电子显微镜（SEM）、傅里叶变换红外光谱（FT-IR）和差示扫描量热仪（DSC）对包合物的物理化学性质进行全面表征。在 50、60、70 和 80°C 下测定包合物的释放行为，并采用零级或一级动力学、Henderson-Pabis、Peppas、Avrami 和 Page 数学模型进行描述。此外，还采用分子模拟技术鉴定包合物的可能结合模式。
首先，PSD、FT-IR、DSC 和 SEM 的结构表明：（i）CDs 可以有效地包封苎烯分子；（ii）Avrami 和 Page 模型可以很好地模拟释放动力学。其次，在 20 小时后，ICs 的释放速率在早期经历了一个非稳态阶段，逐渐变为几乎恒定的阶段。除了 γ-CD/myrcene 的释放属于一级动力学外，其余三种 ICs 的释放模型均属于扩散模式。第三，优化结构的计算结合能为α-CD/myrcene、β-CD/myrcene、γ-CD/myrcene 和 HP-β-CD/myrcene ICs 分别为-4.28、-3.82、-4.04 和-3.72 kcal/mol。最后，根据稳定性和释放特性，苎烯与α-CD 和β-CD 的包封效果较好。
CDs 的类型对苎烯的包封有很大的影响，通过与合适的 CDs 络合可以提高稳定性。通过动力学参数和分子建模，可以有效地解释客体分子与 CD 分子的结合行为和客体分子的释放特征。本研究可为筛选合适的壳基质提供有效的依据和指导。
