Advanced Science
·
2021
·Vol. 8
·期 8
·2003941
·
IF 16.806
Xian Sun,Xiaochuan Zhang,Xiaohong Ren,Hongyu Sun,Li Wu,Caifen Wang,Xiaohui Ye,Peter York,Zhaobing Gao,Hualiang Jiang,Jiwen Zhang,Xianzhen Yin
The effective pulmonary deposition of inhaled particulate carriers loaded with drugs is a prerequisite for therapeutic effects of drug delivery via inhalation route. Revealing the sophisticated lung scaffold and intrapulmonary distribution of particles at three-dimensional (3D), in-situ, and single-particle level remains a fundamental and critical challenge for dry powder inhalation in pre-clinical research. Here, taking advantage of the micro optical sectioning tomography system, the high-precision cross-scale visualization of entire lung anatomy is obtained. Then, co-localized lung-wide datasets of both cyto-architectures and fluorescent particles are collected at full scale with the resolution down to individual particles. The precise spatial distribution pattern reveals the region-specific distribution and structure-associated deposition of the inhalable particles in lungs, which is undetected by previous methods. Overall, this research delivers comprehensive and high-resolution 3D detection of pulmonary drug delivery vectors and provides a novel strategy to evaluate materials distribution for drug delivery.
研究领域:
药剂学
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生物医学工程
·
肺科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 4.3
Qinxiu Zhang,Genju Li,Guozhi Zhao,Chongzheng Yan,Huaiyou Lv,Yaqing Fu,Yuhan Li,Zhongxi Zhao
Orally marketed products nintedanib (NDNB) and pirfenidone (PFD) for pulmonary fibrosis (PF) are administered in high doses and have been shown to have serious toxic and side effects. NDNB can cause the elevation of galectin-3, which activates the NF-κB signaling pathway and causes the inflammatory response. S-allylmercapto-N-acetylcysteine (ASSNAC) can alleviate the inflammation response by inhibiting the TLR-4/NF-κB signaling pathway. Therefore, we designed and prepared inhalable ASSNAC and NDNB co-loaded liposomes for the treatment of pulmonary fibrosis. The yellow, spheroidal co-loaded liposomes with a particle size of 98.32±1.98 nm and zeta potential of -22.5 ± 1.58 mV were produced. The aerodynamic fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of NDNB were >50 % (81.14 %±0.22 %) and <5 μm (1.79 μm±0.06 μm) in the nebulized liposome solution, respectively. The results showed that inhalation improved the lung deposition and retention times of both drugs. DSPE-PEG 2000 in the liposome formulation enhanced the mucus permeability and reduced phagocytic efflux mediated by macrophages. ASSNAC reduced the mRNA over-expressions of TLR-4, MyD88 and NF-κB caused by NDNB, which could reduce the NDNB's side effects. The Masson's trichrome staining of lung tissues and the levels of CAT, TGF-β1, HYP, collagen III and mRNA expressions of Collagen I, Collagen III and α-SMA in lung tissues revealed that NDNB/Lip inhalation was more beneficial to alleviate fibrosis than oral NDNB. Although the dose of NDNB/Lip was 30 times lower than that in the oral group, the inhaled NDNB/Lip group had better or comparable anti-fibrotic effects to those in the oral group. According to the expressions of Collagen I, Collagen III and α-SMA in vivo and in vitro , the combination of ASSNAC and NDNB was more effective than the single drugs for pulmonary fibrosis . Therefore, this study provided a new scheme for the treatment of pulmonary fibrosis.
研究领域:
药剂学
·
肺病学
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药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 11
·2202622
·
IF 10
Qiyue Wang,Ji Liu,Daquan Chen,Si Miao,Jing Wen,Chang Liu,Shushu Xue,Yang Liu,Qingjie Zhang,Yan Shen
Lung metastatic breast cancer (LMBC) is mainly diagnosed through CT imaging and radiotherapy could be the most common method in the clinic to inhibit tumor proliferation. While the sensitivity of radiotherapy is always limited due to the hypoxic tumor microenvironment and high doses of irradiation easily induce systemic cytotoxicity. Metal-based materials applied as radiosensitizers have been widely investigated to improve efficiency and reduce the doses of irradiation. Herein, it is aimed to overcome these problems by designing biodegradable lipid-camouflaged bismuth-based nanoflowers (DP-BNFs) as both a photo-thermo-radiosensitizer to develop a novel photothermal therapy (PTT) and radiotherapy combination strategy for LMBC treatment. To achieve effective lung deposition, “Cluster Bomb” structure-based DP-BNFs nano-in-micro dry powder inhalation (DP-BNF@Lat-MPs) are formulated through spray-dried technology. The DP-BNFs “cluster” in the microsphere to improve their tumor-targeted lung deposition with a high fine particle fraction followed by burst releasing of DP-BNFs for targeting delivery and LMBC therapy. The DP-BNF@Lat-MPs exhibit excellent photothermal conversion efficiency, radiotherapy enhancement, and CT imaging ability in vitro, which synergistically inhibit cell proliferation and metastasis. In vitro and in vivo data prove that combining PTT and radiotherapy with DP-BNF@Lat-MPs as a thermo-radio dual-sensitizer significantly enhances LMBC tumor metastasis inhibition with good biocompatibility and low toxicity.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
医学影像
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2016
·
IF 0
Lifei Zhu,Miao Li,Xiaoyan Liu,Lina Du,Yiguang Jin
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic- co -glycolic)acid (PLGA) large porous microparticle (LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10 µm, the aerodynamic diameter of the spheres was only 2.72 µm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGA LPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
呼吸科医学
✓ 已验证
产品关联
DOI
PubMed
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