Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Department of Chemical Engineering, Arizona State University, Tempe, AZ, 85284, USA.
Drug Deliv Transl Res. 2021 Jun;11(3):1144-1155. doi: 10.1007/s13346-020-00837-x.
Generating formulations for the delivery of a mixture of natural compounds extracted from natural sources is a challenge because of unknown active and inactive ingredients and possible interactions between them. As one example, natural cranberry extracts have been proposed for the prevention of biofilm formation on dental pellicle or teeth. However, such extracts may contain phenolic acids, flavonol glycosides along with other constituents like coumaroyl iridoid glycosides, flavonoids, alpha-linolenic acid, n-6 (or n-3) fatty acids, and crude fiber. Due to the presence of a variety of compounds, determining which molecules (and how many molecules) are essential for preventing biofilm growth is nontrivial to ascertain. Therefore, a formulation that could contain natural, unrefined, cranberry extract (with all its constituent compounds) at high loading would be ideal. Accordingly, we have generated several candidate formulations including poly(lactic-co-glycolic) acid (PLGA)-based microencapsulation of cranberry extract (CE15) as well as formulations including stearic acid along with polyvinylpyrrolidone (PVP) or Ethyl lauroyl arginate (LAE) complexed with cranberry extracts (CE15). We found that stearic acid in combination with PVP or LAE as excipients led to higher loading of the active and inactive compounds in CE15 as compared with a PLGA microencapsulation and also sustained release of CE15 in a tunable manner. Using this method, we have been able to generate two successful formulations (one preventative based, one treatment based) that effectively inhibit biofilm growth when incubated with saliva. In addition to cranberry extract, this technique could also be a promising candidate for other natural extracts to form controlled release systems.Graphical abstract.
从天然来源提取的天然化合物混合物的制剂的开发具有挑战性，因为未知的活性和非活性成分以及它们之间可能的相互作用。例如，天然蔓越莓提取物已被提议用于预防牙菌斑或牙齿上生物膜的形成。然而，这种提取物可能含有酚酸、黄酮醇糖苷，以及其他成分，如肉桂酰类环烯醚萜糖苷、类黄酮、α-亚麻酸、n-6（或 n-3）脂肪酸和粗纤维素。由于存在多种化合物，确定哪些分子（以及多少分子）对于预防生物膜生长是必不可少的，这一点并不简单。因此，一种能够包含天然、未精制的蔓越莓提取物（及其所有成分化合物）高负载的制剂将是理想的。因此，我们已经生成了几种候选制剂，包括聚（乳酸-共-乙醇酸）（PLGA）包封蔓越莓提取物（CE15）的微胶囊以及包含硬脂酸以及聚乙烯吡咯烷酮（PVP）或月桂酰精氨酸乙酯（LAE）与蔓越莓提取物（CE15）复合的制剂。我们发现，硬脂酸与 PVP 或 LAE 作为赋形剂结合使用，与 PLGA 微胶囊相比，可使 CE15 中的活性和非活性化合物的负载量更高，并且以可调节的方式持续释放 CE15。使用这种方法，我们已经能够生成两种成功的制剂（一种基于预防，一种基于治疗），当与唾液孵育时，这些制剂有效地抑制生物膜的生长。除了蔓越莓提取物之外，这种技术也可能是其他天然提取物形成控制释放系统的有前途的候选者。
