用于哮喘治疗的孢子启发式吸入给药系统
2025/08/31
摘要
肺部药物递送效率对于靶向肺部疾病的吸入疗法至关重要。然而，当前的吸入载体在克服肺部屏障方面面临挑战，导致递送效率不足。为解决这一局限，我们开发了一种“孢子启发式”策略。灵芝孢子（GLS）具有双重递送优势：其天然形态有助于支气管 - 肺泡沉积，同时能避开巨噬细胞的内吞作用，增强肺部滞留性。利用这些特性，通过精确碳化制备了一种名为碳化灵芝孢子（cGLS）的仿生载体，该载体保留了孢子的天然形态优势，同时降低了免疫反应并提高了载药量。随后，我们通过负载哮喘药物布地奈德（BUD）开发了孢子启发式吸入给药系统BUD - cGLS，该系统有助于精确调控“沉积 - 逃逸 - 释放”过程。在卵清蛋白（OVA）诱导的哮喘模型中，BUD - cGLS显著降低了气道阻力，抑制了黏蛋白分泌，并减少了炎性细胞因子。总体而言，这些发现凸显了这种孢子启发式载体作为一种有前景的吸入平台，用于递送药物治疗哮喘和其他肺部疾病的潜力。
Spore-inspired inhalation drug delivery system for asthma therapy
Mengqi Tong, Xi Kuang, Qiaoying Jiang, Gaoxiang Li, Lulu Jin, Yihao Ye, Yi Pan, Yang Zhu, Xiaozhou Mou, Zhengwei Mao, Yueliang Zheng
Abstract
The delivery efficiency of drugs in the lung is crucial for inhaled therapies targeting pulmonary diseases. However, current inhalation carriers face challenges overcoming pulmonary barriers, leading to insufficient delivery efficiency. To tackle this limitation, we have developed a "spore-inspired" strategy. Ganoderma lucidum spores (GLS) provide dual delivery advantages: their natural morphology promotes bronchial-alveolar deposition while evading macrophage endocytosis, enhancing pulmonary retention. Using these features, a biomimetic carrier called carbonized GLS (cGLS) is created through precise carbonization, which preserves the spores' natural morphological benefits while reducing the immune response and increasing drug-loading capacity. Subsequently, we develop the spore-inspired inhalation drug delivery system BUD-cGLS by loading the asthma medication budesonide (BUD), which facilitates accurate regulation of the "deposition-escape-release" process. In the OVA-induced asthma model, BUD-cGLS significantly reduces airway resistance, suppresses mucin secretion, and decreases inflammatory cytokines. Overall, these findings highlight the potential of this spore-inspired carrier as a promising inhalation platform for delivering drugs to treat asthma and other pulmonary diseases.
肺部药物递送效率对于靶向肺部疾病的吸入疗法至关重要。然而，当前的吸入载体在克服肺部屏障方面面临挑战，导致递送效率不足。为解决这一局限，我们开发了一种“孢子启发式”策略。灵芝孢子（GLS）具有双重递送优势：其天然形态有助于支气管 - 肺泡沉积，同时能避开巨噬细胞的内吞作用，增强肺部滞留性。利用这些特性，通过精确碳化制备了一种名为碳化灵芝孢子（cGLS）的仿生载体，该载体保留了孢子的天然形态优势，同时降低了免疫反应并提高了载药量。随后，我们通过负载哮喘药物布地奈德（BUD）开发了孢子启发式吸入给药系统BUD - cGLS，该系统有助于精确调控“沉积 - 逃逸 - 释放”过程。在卵清蛋白（OVA）诱导的哮喘模型中，BUD - cGLS显著降低了气道阻力，抑制了黏蛋白分泌，并减少了炎性细胞因子。总体而言，这些发现凸显了这种孢子启发式载体作为一种有前景的吸入平台，用于递送药物治疗哮喘和其他肺部疾病的潜力。
（中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校）
（Bioact Mater. 2025 Aug 6:53:801-818. doi: 10.1016/j.bioactmat.2025.07.045. eCollection 2025 Nov.）
Spore-inspired inhalation drug delivery system for asthma therapy
Mengqi Tong, Xi Kuang, Qiaoying Jiang, Gaoxiang Li, Lulu Jin, Yihao Ye, Yi Pan, Yang Zhu, Xiaozhou Mou, Zhengwei Mao, Yueliang Zheng
Abstract
The delivery efficiency of drugs in the lung is crucial for inhaled therapies targeting pulmonary diseases. However, current inhalation carriers face challenges overcoming pulmonary barriers, leading to insufficient delivery efficiency. To tackle this limitation, we have developed a "spore-inspired" strategy. Ganoderma lucidum spores (GLS) provide dual delivery advantages: their natural morphology promotes bronchial-alveolar deposition while evading macrophage endocytosis, enhancing pulmonary retention. Using these features, a biomimetic carrier called carbonized GLS (cGLS) is created through precise carbonization, which preserves the spores' natural morphological benefits while reducing the immune response and increasing drug-loading capacity. Subsequently, we develop the spore-inspired inhalation drug delivery system BUD-cGLS by loading the asthma medication budesonide (BUD), which facilitates accurate regulation of the "deposition-escape-release" process. In the OVA-induced asthma model, BUD-cGLS significantly reduces airway resistance, suppresses mucin secretion, and decreases inflammatory cytokines. Overall, these findings highlight the potential of this spore-inspired carrier as a promising inhalation platform for delivering drugs to treat asthma and other pulmonary diseases.
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