Pharmaceutics
·
2023
·Vol. 15
·期 3
·866
·
IF 5.4
Lei Shu,Wenhua Wang,Chon-iong Ng,Xuejuan Zhang,Ying Huang,Chuanbin Wu,Xin Pan,Zhengwei Huang
Background: Delivery of inhalable nanoparticles through metered-dose inhalers (MDI) is a promising approach to treat lung disease such as asthma and chronic obstructive pulmonary disease. Nanocoating of the inhalable nanoparticles helps in stability and cellular uptake enhancement but complicates the production process. Thus, it is meaningful to accelerate the translation process of MDI encapsulating inhalable nanoparticles with nanocoating structure. Methods: In this study, solid lipid nanoparticles (SLN) are selected as a model inhalable nanoparticle system. An established reverse microemulsion strategy was utilized to explore the industrialization potential of SLN-based MDI. Three categories of nanocoating with the functions of stabilization (by Poloxamer 188, encoded as SLN(0)), cellular uptake enhancement (by cetyltrimethylammonium bromide, encoded as SLN(+)), and targetability (by hyaluronic acid, encoded as SLN(−)) were constructed upon SLN, whose particle size distribution and zeta-potential were characterized. Subsequently, SLN were loaded into MDI, and evaluated for the processing reliability, physicochemical nature, formulation stability, and biocompatibility. Results: The results elucidated that three types of SLN-based MDI were successfully fabricated with good reproducibility and stability. Regarding safety, SLN(0) and SLN(−) showed negligible cytotoxicity on cellular level. Conclusions: This work serves as a pilot study for the scale-up of SLN-based MDI, and could be useful for the future development of inhalable nanoparticles.Keywords:inhalation;solid lipid nanoparticle;metered-dose inhaler;pilot study;nanocoating
研究领域:
药剂学
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纳米技术
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肺医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Muhan Sun,Xiaoxu Jiang,Rui Liu,Deqin Kong,Hao Wu,Zhao Wang,Gang Zheng,Chongmiao Zhang,Weihua Yu
Sewage effluent and reclaimed water usually contain elevated concentrations of bacteria-derived endotoxins, which may have serious public health implications upon exposure. Both conventional disinfection methods, such as chlorine, ultraviolet, and ozone disinfection, and the new potassium ferrate disinfection process have limited endotoxin removal capacity. Therefore, it is necessary to find new methods of removing endotoxins. In this study, we investigated the effects of ultraviolet/ferrate (UV/Fe(VI)) combination treatment on endotoxin elimination and inhalation hazard control. Our results indicate that UV or Fe(VI) alone cannot sufficiently eliminate endotoxins but can instead exacerbate endotoxin release during bacterial inactivation. However, the UV/Fe(VI) combination rapidly eliminated approximately 85.6 % of both pure and bacteria-derived endotoxins. The optimal conditions for this disinfection process were determined to be 10 mg/L of Fe(VI) and 160 μW/cm 2 of UV exposure for 15 min. Furthermore, the pH value, bicarbonate (HCO 3 – ), humic acid, and turbidity were determined as potential factors that may affect UV/Fe(VI)-mediated endotoxin removal in reclaimed water. The potential mechanism underlying UV/Fe(VI)-induced endotoxin degradation involves several strongly oxidizing species, among which Fe(IV)/Fe(V) is regarded as the primary contributor, followed by the superoxide anion ( • O 2 – ) and hydroxyl ( • OH) radicals. These active substances induce the breakdown of the endotoxin molecular structure into smaller, non-toxic fragments. Furthermore, pure endotoxins, Escherichia coli , and Pseudomonas aeruginosa were disinfected with UV/Fe(VI), and then these aerosolized samples were inhaled exposed to mice. Our results demonstrated that combined use of UV and Fe(VI), rather than administration alone, remarkably blunted bacterial- and endotoxin-induced lung injury. In conclusion, these results demonstrate that the UV/Fe(VI) approach successfully eliminates endotoxins and related inhalation hazards from reclaimed water.
研究领域:
环境科学
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公共卫生
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微生物学
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水处理
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产品关联
DOI
高影响因子
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
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肺科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Xianjie Li,Caixia Wu,Ping Yang,Yanxi Li,Shuai Wang,Dan Cai,Ran Wei,Jinfeng Gao,Xuemei Wen,Jieping Luo,Rui Wang,Xueyuan Bai,Shen Chen,Ping Guo
The burden of N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its oxidized products on human health can no longer be ignored due to the detection types and concentrations in the environment continue to increase. Environmental ozone (O 3 ) and ultraviolet A (UVA) may induce ozonation and photoaging of 6PPD to produce toxic products. However, the impact of specific environmental conditions on the aging and toxic effects of 6PPD is unclear. This study investigated the aging effects of O 3 and UVA on 6PPD, and compared the repeated inhalation toxicity of differently aging 6PPDs in C57BL/6 male mice. The result showed that UVA and O 3 accelerated 6PPD aging, and the aging products varied depending on the O 3 and irradiation conditions. After 10 weeks of inhalation intoxication at human comparable level, mice exhibited significant neurobehavior alterations, respiratory dysfunction, and DNA damage in the blood, showing significant heterogeneity among groups. Notably, 6PPD treated with perozonation and UVA aging may be the most toxic. The study suggests inhalation health risks of transportation derived tire pollutants under the influence of ground-level ozone and ultraviolet light need more attention, and provides new insights into risk assessment and pollution control of 6PPD and other pollutants from the perspective of environmental factors.
研究领域:
环境科学
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毒理学
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医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Tianjiao Ma,Lei Yang,Binmei Zhang,Xin Lv,Feifei Gong,Wei Yang
Aims Doxorubicin is a drug widely used in clinical cancer treatment, but severe cardiotoxicity limits its clinical application. Autophagy disorder is an important factor in the mechanism of doxorubicin-induced cardiac injury. As the smallest molecule in nature, hydrogen has various biological effects such as anti-oxidation, anti-apoptosis and regulation of autophagy. Hydrogen therapy is currently considered to be an emerging therapeutic method, but the effect and mechanism of hydrogen on doxorubicin-induced myocardial injury have not been determined. The purpose of this study was to investigate the protective effect of hydrogen inhalation on doxorubicin-induced chronic myocardial injury and its effect and mechanism on autophagy. Methods In this study, we established a chronic heart injury model by intraperitoneal injection of doxorubicin in rats for 30 days, accumulating 20 mg/kg. The effect of hydrogen inhalation on the cardiac function in rats was explored by echocardiography, Elisa, and H&E staining. To clarify the influence of autophagy, we detected the expression of LC3 and related autophagy proteins in vivo and in vitro by immunofluorescence and western blot.In order to further explore the mechanism of autophagy, we added pathway inhibitors and used western blot to preliminarily investigate the protective effect of hydrogen inhalation on myocardial injury caused by doxorubicin. Results Hydrogen inhalation can improve doxorubicin-induced cardiac function decline and pathological structural abnormalities in rats. It was confirmed by immunofluorescence that hydrogen treatment could restore the expression of autophagy marker protein LC3 (microtubule-associated protein 1 light chain 3) in cardiomyocytes reduced by doxorubicin, while reducing cardiomyocyte apoptosis. Mechanistically, Western blot results consistently showed that hydrogen treatment up-regulated the ratio of p-AMPK (phosphorylated AMP-dependent protein kinase) to AMPK and down-regulated p-mTOR (phosphorylated mammalian target of rapamycin) and mTOR ratio. Conclusions These results suggest that hydrogen inhalation can activate autophagy through the AMPK/mTOR pathway and protect against myocardial injury induced by doxorubicin. Hydrogen inhalation therapy may be a potential treatment for doxorubicin-induced myocardial injury.
研究领域:
医学
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药理学
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心血管科学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2025
·
IF 13
Qu-Nan Wang,Chunzhi Wang,Yán Wāng
Introduction The extensive use of 6PPD in tire rubber has led to its increase in atmospheric tire wear particles. 6PPD reacts with ozone to form 6PPD-quinone (6PPD-Q), a respiratory toxicant enriched in tire and road wear particles. Objectives The aim of this study is to decipher the potential sensitive target organs and toxic actions by inhalation exposure to atmospheric 6PPD-Q. Methods This study employed a mouse inhalation exposure model to simulate environmental levels of 6PPD-Q at three concentrations of 0, 0.14, and 14 mg/m 3 . Using a 28-day exposure period followed by an equivalent recovery phase, we systematically evaluated the toxicological targets and effects of subacute exposure. Results The findings revealed that, compared to pulmonary, cardiovascular, and metabolic organ damage, 6PPD-Q-induced neurotoxicity was more persistent and irreversible, particularly characterized by prolonged anxiety-like behaviors. Histopathological analyses of the basolateral amygdala, using Nissl staining and markers of neuronal aging, indicated substantial neuronal degeneration linked to elevated oxidative stress, identifying this region as a critical target of 6PPD-Q neurotoxicity. Transcriptomic analysis uncovered that the expression of Egr1 , a transcription factor crucial for neuronal plasticity, was markedly dysregulated. Findings of significant downregulation at the gene level and an upward trend in protein expression suggest that Egr1 expression is influenced by translational efficiency, epigenetic modifications, and post-translational regulatory mechanisms. Egr1 dysregulation disrupted downstream networks involving solute carrier proteins and calcium-binding proteins, contributing to aberrant neurobehavioral outcomes. Notably, the elevation of Egr1 protein levels in the basolateral amygdala but not in the cerebral cortex highlights the region-specific nature of 6PPD-Q’s neurotoxic effects. Conclusion This study provides the first insights into the neurotoxicity and irreversibility of inhaled 6PPD-Q exposure, paving the way for future research into the long-term neurological consequences and regulatory mechanisms of 6PPD-Q.
研究领域:
毒理学
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神经科学
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环境健康
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 20
·4702
·
IF 3.267
Nan Zhang,Mu Luo,Lei He,Lei Yao
Gardenia jasminoidesEllis is a famous fragrant flower in China. Previous pharmacological research mainly focuses on its fruit. In this study, the essential oil of the flower of ‘Shanzhizi’, which was a major variety for traditional Chinese medicine use, was extracted by hydro distillation and analyzed by GC-MS. Mouse anxiety models included open field, elevated plus maze (EPM), and light and dark box (LDB), which were used to evaluate its anxiolytic effect via inhalation. The involvement of monoamine system was studied by pretreatment with neurotransmitter receptor antagonists WAY100635, flumazenil and sulpiride. The monoamine neurotransmitters contents in the prefrontal cortex (PFC) and hippocampus after aroma inhalation were also analyzed. The results showed that inhalation ofG. jasminoidesessential oil could significantly elevated the time and entries into open arms in EPM tests and the time explored in the light chamber in LDB tests with no sedative effect. WAY100635 and sulpiride, but not flumazenil, blocked its anxiolytic effect. Inhalation ofG. jasminoidesessential oil significantly down-regulated the 5-HIAA/5-HT in the PFC and reduced the 5-HIAA content in hippocampus compared to the control treatment. In conclusion, inhalation of gardenia essential oil showed an anxiolytic effect in mice. Monoamine, especially the serotonergic system, was involved in its anxiolytic effect.Keywords:Gardenia jasminoides;essential oil;inhalation;anxiolytic effect;serotonergic neurotransmission
研究领域:
药理学
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神经科学
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植物化学
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产品关联
DOI
PubMed
高影响因子
Environmental Systems Research
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2024
·Vol. 13
·期 1
·1-10
·
IF 0
Du Hairong,Zhu Xiaoling,Yao Yunying,Yao Wei
Neonicotinoid insecticides (NNIs), as a new type of insecticide, are widely used in agriculture and daily life. Because of the low volatility of NNIs, few studies have evaluated them in atmospheric particulate matter. In this study, 101 outdoor PM 2.5 samples were collected from the Wuhan urban area from 2019 to 2021, leading to the detection of seven NNIs and three of their metabolites. The detection frequencies of all 10 substances were more than 60%, with DIN (dinotefuran) and IMI (imidacloprid) reaching 100%. DIN (52.4 pg/m 3 ) and IMI (43.0 pg/m 3 ) had higher median concentrations than other substances. Concentration distributions of the four substances ACE (acetamiprid), DIN, IMI, and 5-OH-IMI (5-Hydro-Imidacloprid) exhibited statistically significant differences ( P < 0.05) across the four seasons. Concentration levels of ACE, CLO (clothianidin), and IMI were statistically different between the three years ( P < 0.05). The median concentration of imidacloprid-equivalent total neonicotinoids (IMIeq: generated by the relative potency factor method) was 256.1 pg/m 3 . Finally, the estimated daily intake (EDI) of NNIs via respiration was greater in infants and young children than in the rest of the population, suggesting that infants and young children were more likely to be exposed to the health effects of airborne residual PM 2.5 .
研究领域:
环境科学
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公共卫生
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毒理学
✓ 已验证
DOI
AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 5
·1-14
·
IF 4
Liu Hongting,Sun Yao,Cai Shihao,Zhao Conglu,xu Xiang,Xu Aiguo,Zhou Honggang,Yang Cheng,Gu Xiaoting,Ai Xiaoyu
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause, with few effective therapies available and high mortality rates. Our preceding research indicated that formononetin (FMN) could improve the symptoms of the bleomycin-induced pulmonary fibrosis and be a promising drug against IPF. In this study, an inhalable formononetin-loaded poly(lactic-co-glycolic) acid (PLGA) large porous microspheres (FMN-PLGA-MSs) was prepared by the method of emulsion solvent evaporation. SEM showed that FMN-PLGA-MSs were loose particles existing many pores on the surfaces, and the measured mean geometric diameter was more than 10 µm. The encapsulation efficiency (EE) and drug loading efficiency (DL) were 87.72 ± 6.34% and 4.18 ± 0.30%. FMN in FMN-PLGA-MSs could be rapidly released within 2 h and sustainably released for 21 d. Cell tests and q-RT-PCR tests showed that FMN could inhibit the activation of fibroblasts and the deposition of extracellular matrix (ECM) by acting on the TGF-β1/Smad3 signaling pathway. FMN-PLGA-MSs showed higher antifibrotic effects than free FMN oral administration in the pulmonary fibrosis models of mice, remarkably improving pulmonary function, decreasing hydroxyproline levels, and attenuating lung injuries. By formulating formononetin into microsphere preparations, its solubility can be significantly enhanced, enabling effective pulmonary drug delivery. This approach not only improves lung targeting but also reduces systemic toxicity. Additionally, it facilitates superior lung deposition and extends the retention time of the formononetin within the lungs. Taken together, FMN-PLGA-MSs may be a promising inhaled medication for the treatment of IPF. Graphical Formononetin (FMN) can improve the symptoms of idiopathic pulmonary fibrosis (IPF). Large porous microparticle can improve lung retention and lung targeting. FMN is loaded in poly(lactic-co-glycolic)acid (PLGA) to get microspheres (FMN-PLGA-MSs) for intratracheal instillation treatment of IPF. FMN-PLGA-MSs remarkably improved pulmonary function, decreased hydroxyproline, and attenuated lung injuries. FMN-PLGA-MSs are promising intratracheal instillation medication for the treatment of IPF.
研究领域:
药学
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呼吸病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2025
·
IF 8.1
Jiming Ke,Shenao Li,Miaomiao Zi,Jing Zhang,Shan Huang,Wenhui Luo,Hailun Han,Jiwen Zhang,Can Peng
Acute lung injury (ALI) is a lung disease characterized by pulmonary edema caused by an excessive inflammatory response within the lungs and disruption of the alveolar capillary barrier, with a high morbidity and mortality rate in critically ill patients. Dry powder inhalers (DPI) are an effective way of administering medication to improve efficacy, and inhalation administration not only improves efficacy but also increases the bioavailability of the drug. Synephrine, a natural ingredient derived from the fruit of the citrus plant in the Brassicaceae family, has anti-inflammatory and antioxidant properties. In the present study, we prepared a synephrine dry powder inhaler (SYN-DPI) by anti-solvent precipitation method and evaluated it in vivo and in vitro. The in vitro results show that SYN-DPI has low hygroscopicity and good aerodynamic properties. The in vitro and in vivo efficacy results showed that SYN-DPI not only had low toxicity but also possessed good anti-inflammatory and antioxidant capacity, which could significantly reduce inflammation, oxidative stress, and lung injury. Pharmacokinetic results showed that inhalation administration significantly increased SYN bioavailability. In conclusion, this study provides inhalation administration of synephrine as an inhalable formulation that can be used to improve ALI.
研究领域:
药理学
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呼吸病学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2012
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IF 3.35
Yinhe Tan,Zhiwen Yang,Xin Pan,Meiwan Chen,Min Feng,Lili Wang,Hu Liu,Ziyun Shan,Chuanbin Wu
The objective of this study was to investigate the stability and aerosolization of pressurized metered dose inhalers (pMDIs) containing thymopentin nanoparticles . Thymopentin nanoparticles, fabricated by a bottom-up process, were suspended in hydrofluoroalkane (HFA) 134a together with cineole and/or n -heptane to produce pMDI formulations. The stability study of the pMDIs obtained was carried out at ambient temperature for 6 months. The amount of thymopentin and the aerosolization properties of pMDIs were determined using high-performance liquid chromatography (HPLC) and a twin-stage impinger (TSI), respectively. Based on the results, thymopentin nanoparticles were readily suspended in HFA 134a with the aid of cineole and/or n -heptane to form physically stable pMDI formulations, and more than 98% of the labeled amount of thymopentin and over 50% of the fine particle fraction (FPF) of the pMDIs were achieved. During storage, it was found that for all pMDIs more than 97% of the labeled amount of thymopentin and FPF greater than 47% were achieved. Moreover, the size of thymopentin nanoparticles in propellant containing cineole and n -heptane showed little change. It is, therefore, concluded that the pMDIs comprising thymopentin nanoparticles developed in this study were stable and suitable for inhalation therapy for systemic action.
研究领域:
药剂学
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Jiadong Pang,Xiaoyu Chen,Zhijun Lin,Shuo Yao,Wanyan Wang,Hong Wu,Wei Xing,Jiang Yang
Anaplastic lymphoma kinase (ALK) oncogenic fusions are an infamously evolving target in ALK fusion-positive (ALK + ) non-small cell lung cancer (NSCLC). RNA interference (RNAi) is a potential alternative to small-molecule ALK inhibitors but suffers from poor cellular delivery and low stability, restricting sustained on-target therapeutic efficacy. To attain non-invasive direct RNAi at target sites in the lungs, inhalable vehicles are demanded to shield unstable siRNA from degradation in alkaline pleural fluid and to shuttle siRNA in the acidic tumor microenvironment. Here, we chemically synthesize a universal polyethylene glycol-poly(β-amino esters)-histidine(PEG-PBAE-His, PPH) system that enables siRNA-directed ALK gene silencing in ALK + NSCLC with controlled release. The rational design of PEGylated polycationic PPH integrates the non-ionic nature, inertness, stealth effect, and low immunogenicity of PEG coronae with dual positively-charged PBAE and His to encapsulate siRNA payloads through enhanced electrostatic complexations. The assembled polyplexes with low polydispersity are overall anionic in alkaline pleural fluid and reversed into cationic charges at acidic pH, facilitating cellular uptake and lysosomal pH-governed release. The PPH-directed delivery significantly improves siRNA stability and ALK sequence-specific knockdown in H3122 cells, with a transfection efficiency comparable to commercial polyethylenimine but with lower cytotoxicity. The ALK-centric RNAi therapy prohibits cancer clonogenicity, migration, and invasion and induces potent growth inhibition in ALK + NSCLC xenografts through inhalation. The inhalable polyplexes represent a transformative delivery platform that combines pH-responsive targeting, enhanced stability, and low toxicity, addressing critical limitations of existing siRNA delivery systems.
研究领域:
肿瘤学
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分子生物学
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药剂学
✓ 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）