Qiu Kunyu, Anselmo Aaron C
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
ACS Appl Mater Interfaces. 2021 Oct 6;13(39):46282-46290. doi: 10.1021/acsami.1c11785. Epub 2021 Sep 24.
Live microbes such as lactobacilli have long been used as probiotic supplements and, more recently, have been explored as live biotherapeutic products with the potential to treat a range of conditions. Among these microbes is a category of anaerobes that possess therapeutic potential while exhibiting unique oxygen sensitivity and thus requiring careful considerations in the formulation and storage processes. Existing microbial formulation development has focused on facultative anaerobes with natural oxygen tolerance; a few strategies have been reported for anaerobes with demonstrated oxygen intolerance, warranting novel approaches toward addressing the challenges for these oxygen-sensitive anaerobes. Here, we develop a polymeric encapsulation system for the formulation and storage of (), a model anaerobe that loses viability in aerobic incubation at 37 °C within 1 day. We discover that this strain remains viable under aerobic conditions for 14 days at 4 °C, enabling formulation development such as solution casting and air drying in an aerobic environment. Next, through a systematic selection of polymer encapsulants and excipients, we show that encapsulation with poly(vinyl alcohol) (PVA) acts as an oxygen barrier and facilitates long-term storage of , which is partially attributed to reduced generation of reactive oxygen species. Lastly, PVA-based formulations can produce oral capsule-loaded films and edible gummy bears, demonstrating its compatibility with both pharmaceutical and food dosage forms.
诸如乳酸杆菌等活微生物长期以来一直被用作益生菌补充剂，最近，它们还被探索作为具有治疗一系列病症潜力的活生物治疗产品。在这些微生物中，有一类厌氧菌具有治疗潜力，但表现出独特的氧敏感性，因此在制剂和储存过程中需要仔细考虑。现有的微生物制剂开发主要集中在具有天然氧耐受性的兼性厌氧菌上；对于已证明对氧不耐受的厌氧菌，已有一些策略被报道，这就需要新的方法来应对这些对氧敏感的厌氧菌所面临的挑战。在此，我们开发了一种聚合物封装系统，用于制剂和储存（），这是一种模式厌氧菌，在37℃有氧培养条件下1天内就会失去活力。我们发现，该菌株在4℃有氧条件下可存活14天，这使得在有氧环境中进行诸如溶液浇铸和空气干燥等制剂开发成为可能。接下来，通过对聚合物封装剂和辅料的系统筛选，我们表明用聚乙烯醇（PVA）进行封装可作为氧气屏障，并有助于（）的长期储存，这部分归因于活性氧生成的减少。最后，基于PVA的制剂可以生产口服胶囊载药薄膜和可食用小熊软糖，证明了其与药物剂型和食品剂型的兼容性。
