DRUG DELIVERY
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2015
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IF 2.558
Hailong Zhang,Xiaoyan Huang,Ya Sun,Jianfeng Xing,Akira Yamamoto,Yang Gao
Effects of chitosan oligomers with different types and varying concentrations on the intestinal and pulmonary absorptions of calcitonin were investigated in rats by an in situ closed loop method and an in vivo pulmonary absorption experiment, respectively. Various chitosan oligomers demonstrated different efficiencies in improving the intestinal and pulmonary absorptions of calcitonin, and chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the greatest absorption enhancing effect. Moreover, pharmacodynamic parameters of calcitonin after its coadministration intrapulmonarily with various chitosan oligomers were consistently larger than that in the intestinal delivery, indicating the superior potential of pulmonary administration for systemic delivery of calcitonin. Furthermore, various chitosan oligomers neither obviously increased release amounts of protein nor activities of lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), revealing the safety of these chitosan oligomers to lung tissue. In addition, bioadhesions of various chitosan oligomers were well consistent with their absorption enhancing effects in the absorption experiment, suggesting the contribution of mucoadhesive properties of chitosan oligomers to their absorption improving effects. Taken together, chitosan oligomers, especially chitosan hexamer, can effectively improve the intestinal and pulmonary absorptions of calcitonin partly due to the mucoadhesion between positive chitosan oligomers and negative mucus in the membrane.
研究领域:
药剂学
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药物递送
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2018
·
IF 8.806
Qiyue Wang,Gujie Mi,Daniel Hickey,Yanan Li,Jiasheng Tu,Thomas J. Webster,Yan Shen
Pneumonia is a major contributor to infection-based hospitalizations and deaths in the United States. Antibiotics such as azithromycin (AZM), although effective at managing pneumonia, often suffer from off-target diffusion and poor bioavailability when administered orally or via intravenous injection. The formation of biofilms at the disease sites makes the treatment more complicated by protecting bacteria from antimicrobial agents and thus necessitating a much higher dosage of antibiotics to eradicate the biofilms. As such, targeted pulmonary delivery of antibiotics has emerged as a promising alternative by providing direct access to the lung while also allowing higher local therapeutic concentrations but minimal systemic exposure. In this study, AZM was encapsulated in N-fumaroylated diketopiperazine (FDKP) microparticles for efficient pulmonary delivery. Both in vitro and in vivo results demonstrated that AZM@FDKP-MPs administered via intratracheal insufflation achieved at least a 3.4 times higher local concentration and prolonged retention times compared to intravenous injection and oral administration, suggesting their potential to better manage bacterial pneumonia.
研究领域:
药学
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微生物学
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Yang Gao,Guangli Liao,Shucong Wang,Ya Sun,Xin Long,Yan Ma,Hailong Zhang
This research aims to investigate the potential of N-[4-[1-(3-Aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl]-1,3-propanediamine (SPM-NONOate) for promoting the absorption of poorly absorbed macromolecules delivered by intrapulmonary route. Influence of SPM-NONOate on the drug absorption was characterized by using a series of fluorescein isothiocyanate-labeled dextrans (FDs) as affordable models of hydrophilic macromolecules with established tools for quantitative analysis. SPM-NONOate increased concentration-dependently within 1–10 mM the pulmonary absorptions of FDs in rats. Moreover, this promoting effect varied with the molecular weight of FDs, and the largest absorption enhancement effect was obtained for FD70. SPM-NONOate also showed promising enhancement potential on the absorption of some therapeutic peptides, where obvious hypoglycemic and hypocalcemic effects were observed after intrapulmonary delivery of insulin and calcitionin, respectively, with SPM-NONOate to rats. The safety of SPM-NONOate was confirmed based on measurement of some biological markers in bronchoalveolar lavage fluid (BALF) of rats. Additionally, mechanism underling the absorption enhancement action of SPM-NONOate was explored by combinatorial administration of FD4 and SPM-NONOate with various scavengers and generator to rat lungs. Results indicated that NO released from SPM-NONOate induced the enhancement in the drug absorption, and peroxynitrate , a NO metabolite, possibly participated in the absorption enhancing action of SPM-NONOate.
研究领域:
药理学
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药物递送系统
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生物化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Zhengwei Huang,Ling Lin,Cushla McGoverin,Hu Liu,Lili Wang,Qi (Tony) Zhou,Ming Lu,Chuanbin Wu
Formulating poorly water-soluble drug, itraconazole (ITZ), as dry powder inhaler (DPI) may be more effective for the treatment of invasive pulmonary Aspergillosis than intravenous injection and oral administration. It is necessary to improve the dissolution of ITZ because the alveolar lining fluid is limited and thus the dissolution of ITZ in the lung may be slow and incomplete. However, too fast dissolution may result in over-absorption into the circulation and thus insufficient distribution in the lung. The purpose of this study is to understand the relationship between in-vitro dissolution and in-vivo distribution of ITZ from DPI formulations. Two DPI formulations (F1 and F2) with identical compositions and similar aerodynamic behaviors were fabricated by hot melt extrusion and thus jet-milling. ITZ was formulated with mannitol as fine solid crystal suspension system to effectively improve its dissolution. In-vitro dissolution tests and in-vivo pharmacokinetic studies indicated that F1 released faster than F2 under both sink and non-sink conditions, but exhibited a lower lung retention and higher plasma absorption than F2. These results suggested that although dissolution enhancement of poorly water-soluble drugs in pulmonary delivery may be necessary to overcome problems such as local irritation and quick elimination by macrophages, it may have an impact on the distribution of the drug between the lung and the plasma. A balance between airway dissolution and systemic absorption should be taken into consideration when developing DPI formulations of poorly water-soluble ITZ.
研究领域:
药剂学
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药物代谢动力学
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医学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 3
·329
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IF 5.5
Jinniu Zhang,Yun Huang,Wenhao Shen,Yixing Zeng,Yingjing Miao,Nianping Feng,Tianyuan Ci
Objectives:Liposomes are a promising drug carrier for inhaled delivery systems and their physical parameters could influence therapeutic efficacy significantly. This study was designed to answer the specific question of the proper surface charge of liposomes in pulmonary inhalation, as well as to study the synergistic anti-inflammation efficacy between drugs.Methods:In this work, a series of drug-loaded liposomes with different surface charges (from negative to positive) were prepared, and several in vitro and in vivo assays, including cytotoxicity, hemolysis assay, mucus penetration and lipopolysaccharide (LPS)-induced pneumonia model test, were adopted to evaluate the anti-inflammation efficacy and biocompatibility of the above liposomes.Results:Compared with cationic liposomes, anionic liposomes are capable of better mucus penetration and good biocompatibility (low cytotoxicity, better blood compatibility and mild tissue inflammation), but with poor cellular uptake by immune cells. In specific, even when the liposome surface charge was only +2.6 mV, its cytotoxicity and blood hemolysis reached around 20% and 15%, respectively. Furthermore, there was no significant difference in biocompatibility between anionic liposomes (−25.9 vs. −2.5 mV), but a slightly negative-charged liposome exhibited better cellular uptake.Conclusions:Thus, slightly negative-charged liposomes (−1~−3 mV) could be a well inhaled drug carrier considering both efficacy and biocompatibility. In an LPS-induced pneumonia mouse model, the drug-loaded liposomes achieved better anti-inflammatory efficacy compared with free drugs.
研究领域:
药剂学
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医学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Lei Chen,Xiaomei Wang,Mengping Chen,Qiwen Sun,Yemeng Chen,Xiaojie Zhang,Rui Hong,Yigong Xu,Jingwen Guan,Sheng Hong,Dehan Cao,Tingfeng Sun,Ximeng Li,Lanhua Chen,Juan Diwu
The limited availability of effective agents for removing actinides from the lungs significantly restricts the effectiveness of medical treatments for nuclear emergencies. Inhalation is the primary route of internal contamination in 44.3% of actinide-related accidents, leading to the accumulation of radionuclides in the lungs and resulting in infections and potential tumor formation (tumorigenesis). This study focuses on the synthesis of a nanometal−organic framework (nMOF) material called ZIF-71-COOH, which is achieved by post-synthetic carboxyl functionalization of ZIF-71. The material demonstrates high and selective adsorption of uranyl, while also exhibiting increased particle size (≈2100 nm) when it aggregates in the blood, enabling passive targeting of the lungs through mechanical filtration. This unique property facilitates the rapid enrichment and selective recognition of uranyl, making nano ZIF-71-COOH highly effective in removing uranyl from the lungs. The findings of this study highlight the potential of self-aggregated nMOFs as a promising drug delivery system for targeted uranium decorporation in the lungs.
研究领域:
放射医学
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材料科学
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纳米技术
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2018
·Vol. 22
·期 7
·3514-3525
·
IF 4.302
Wenhui Cui,Zhihui Zhang,Panpan Zhang,Jiao Qu,Cheng Zheng,Xiaoting Mo,Wencheng Zhou,Liang Xu,Hongwei Yao,Jian Gao
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway. Interestingly, these effects of LiCl were not observed in Nrf2 −/− mice exposed to elastase. In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression up-regulated, whereas Wnt3a knockdown further down-regulated the levels of Nrf2 and its target proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) by CSE treatment. In contrast, Nrf2 deficiency did not have any effects on Wnt/β-catenin pathway in mouse lungs and NHBE cells. Both elastase and CSE exposures reduced AMPK phosphorylation. A specific AMPK activator metformin increased Wnt3a, β-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE. Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells. In conclusion, Nrf2 mediates the protective effects of both Wnt3a/β-catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema. These findings provide potential therapeutic targets for the intervention of COPD/emphysema.
研究领域:
医学
·
分子生物学
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药理学
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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 5
·1-18
·
IF 4
Yang Hongyu,Qin Jianpeng,Wang Yuou,Li Ji,Wang Dongkai
Pulmonary bacterial infections are a common disease, with erythromycin being a first-line treatment. However, conventional erythromycin tablets and injectables exhibit limited therapeutic efficacy and are associated with severe gastrointestinal side effects. Additionally, injectable formulations suffer from poor patient compliance. Dry powder inhaler (DPI) offers superior pulmonary targeting, circumvent first-pass metabolism, and are portable, enhancing patient adherence. In this study, we successfully developed a ternary inhalable erythromycin dry powder formulation (Ery-DPI). The Quality by Design (QbD) approach was employed to establish a design space for erythromycin micronization and to optimize the formulation. The physicochemical properties and fine particle fraction of the erythromycin DPI were evaluated through in vitro experiments. The final formulation, composed of α-lactose, mannitol, and erythromycin in a ratio of 1:0.2:2 (v/v/v), exhibited an FPF of 70 ± 3%. In vivo studies demonstrated that, compared to intravenous administration, Ery-DPI achieved higher and more stable local drug exposure in the lungs. Overall, our study provides new insights into pulmonary drug delivery strategies for treating bacterial infections. Graphical
研究领域:
药剂学
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呼吸病学
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药物化学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Quanyi Liu,Sheng Zhao,Yihong Zhang,Xueying An,Quan Wang,Sirong Li,Anqi Lin,Yan Du,Hui Wei
Serious lung diseases and other health problems caused by tobacco consumption are becoming more and more prominent all over the world. Scavenging the excessive harmful free radicals in cigarette smoke is proven to be an effective method in reducing the above problems. Carbon-based nanozymes have been widely studied due to their ability of scavenging free radicals. Accordingly, the biochar derived from silkworm excrement was reported as a nanozyme with free radical scavenging ability. The biochar nanozyme calcination at 900 °C with better free radical scavenging abilities was loaded into commercial cigarette filters for the following free radical scavenging verification in tobacco smoke. Mouse model results reveal the lung tissue could be improved by the addition of biochar nanozyme. This work not only provides an effective approach to reduce the harm caused by tobacco but also provides potential applications to rationally realize low-cost, ease of production, and a wide variety of biochar sources.
研究领域:
环境科学
·
材料科学
·
健康科学
✓ 已验证
DOI
PubMed
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Xiaobo Zhang,Zhengli Zhou,Xiaohui Yang,Lei Huang,Qin Wang,Yi Chen,Kesi Du,Jianqing Peng
To overcome the critical challenge in drug inhalation for pulmonary diseases, we innovatively proposed that polydopamine (PDA) as a surface modification material had great potential to improve the mucus permeation and pulmonary retention of inhalable lipid-based nanocarriers. We prepared PDA coated lipid nanoemulsions/solid lipid nanoparticles/liposomes and systematically evaluated their interactions with mucin and pulmonary retention after inhalation. PDA-coated lipid-based nanocarriers exhibited weaker interactions with mucins, higher mucus permeability and cellular uptake by the respiratory epithelium cells compared to PEGylated lipid-based nanocarriers. However, the pulmonary retention advantage of PDA coating was shown in lipid nanoemulsions (< 50 nm) and solid lipid nanoparticles (< 100 nm). Liposomes (∼ 150 nm) with PEGylation possessed higher pulmonary retention than that coated by PDA. It was suggested that PEGylated liposomes were liable to be phagocytosed by alveolar macrophages due to binding with specific antibodies. Overall, this work suggests that PDA as a surface modification material of inhalable lipid-based nanocarriers holds promise for effective mucus penetration and pulmonary retention.
研究领域:
药剂学
·
生物医学工程
·
呼吸系统疾病治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-15
·
IF 6.518
Zhang Man,Ye Lili,Huang Hao,Cheng Dandan,Liu Kaixin,Wu Wenbo,Shen Fukui,Jiang Zhihong,Hou Yuanyuan,Bai Gang
Background Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. However, developing the formulation of each drug is a time-consuming and laborious task.Results In this study, a universal lung-targeting nanoparticle was designed and constructed. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-d-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone.Conclusion sGP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provide a new lung-targeting therapy option.
研究领域:
药学
·
纳米医学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Yixian Zhou,Yiting Zhao,Boyi Niu,Qiaorong Luo,Yue Zhang,Guilan Quan,Xin Pan,Chuanbin Wu
Pulmonary drug delivery has attracted considerable attention in recent years. However, it is still a major challenge to deliver poorly water-soluble drugs to lungs with good solubility and fine aerodynamic performance. In this study, curcumin was loaded into cyclodextrin-based metal-organic frameworks (CD-MOFs) for pulmonary delivery. Compared with micronized curcumin prepared by jet milling, curcumin-loaded CD-MOFs (Cur-CD-MOFs) exhibited excellent aerodynamic performance, which was attributed to the unique porous structure and lower density of CD-MOFs. The dissolution test showed that the drug release rate of Cur-CD-MOFs was much faster than that of micronized curcumin. The all-atom molecular dynamic simulation showed that curcumin molecules were loaded into the hydrophobic cavities of CD-MOFs or entered into the large hydrophilic cavities to form nanoclusters. The elevated wettability of Cur-CD-MOFs and the unique spatial distribution feature of curcumin in porous interior of CD-MOFs might be favorable for the improved dissolution rate. The DPPH radical scavenging test showed that Cur-CD-MOFs had prominent antioxidant activities. Therefore, CD-MOFs were expected to be promising carriers for pulmonary delivery of poorly water-soluble drugs.
研究领域:
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）