Tran The-Thien, Cheow Wean Sin, Pu Siyu, Park Jin-Won, Hadinoto Kunn
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University Singapore, Singapore 637459, Singapore.
Singapore Institute of Technology, Singapore 138683, Singapore.
Pharmaceutics. 2024 Jul 25;16(8):980. doi: 10.3390/pharmaceutics16080980.
The inhaled delivery of lactic acid bacteria (LAB) probiotics has been demonstrated to exert therapeutic benefits to the lungs due to LAB's immunomodulatory activities. The development of inhaled probiotics formulation, however, is in its nascent stage limited to nebulized LAB. We developed a dry powder inhaler (DPI) formulation of (LGG) intended for bronchiectasis maintenance therapy by spray freeze drying (SFD). The optimal DPI formulation (i.e., LGG: mannitol: lactose: leucine = 35: 45: 15: 5 wt.%) was determined based on the aerosolization efficiency (86% emitted dose and 26% respirable fraction) and LGG cell viability post-SFD (7 log CFU/mL per mg powder). The optimal DPI formulation was evaluated and compared to lyophilized naked LGG by its (1) adhesion capacity and cytotoxicity to human lung epithelium cells (i.e., A549 and 16HBE14o- cells) as well as its (2) effectiveness in inhibiting the growth and adhesion of to lung cells. The optimal DPI of LGG exhibited similar non-cytotoxicity and adhesion capacity to lung cells to naked LGG. The DPI of LGG also inhibited the growth and adhesion of to the lung cells as effectively as the naked LGG. The present work established the feasibility of delivering the LAB probiotic by the DPI platform without adversely affecting LGG's anti- activities.
由于乳酸菌（LAB）的免疫调节活性，吸入乳酸菌益生菌已被证明对肺部具有治疗益处。然而，吸入式益生菌制剂的开发尚处于初期阶段，仅限于雾化的LAB。我们通过喷雾冷冻干燥（SFD）开发了一种用于支气管扩张维持治疗的鼠李糖乳杆菌（LGG）干粉吸入剂（DPI）制剂。基于雾化效率（86%的 emitted dose 和 26%的可吸入部分）以及喷雾冷冻干燥后 LGG 细胞活力（每毫克粉末 7 log CFU/mL）确定了最佳 DPI 制剂（即 LGG：甘露醇：乳糖：亮氨酸 = 35：45：15：5 wt.%）。通过以下方面对最佳 DPI 制剂进行评估并与冻干的裸 LGG 进行比较：（1）对人肺上皮细胞（即 A549 和 16HBE14o-细胞）的粘附能力和细胞毒性，以及（2）抑制铜绿假单胞菌对肺细胞生长和粘附的有效性。LGG 的最佳 DPI 对肺细胞表现出与裸 LGG 相似的无细胞毒性和粘附能力。LGG 的 DPI 在抑制铜绿假单胞菌对肺细胞的生长和粘附方面也与裸 LGG 一样有效。本研究确立了通过 DPI 平台递送 LAB 益生菌的可行性，且不会对 LGG 的抗菌活性产生不利影响。
