BIOMATERIALS
·
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
Pharmaceutics
·
2025
·Vol. 17
·期 3
·329
·
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
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2023
·
IF 3.4
Yanming Wang,Zhang Chenghao,Zhaoli Wu,Xinran Cui,Jinmei Ren,Jingling Tang
Objective Pulmonary aspergillosis, which is a secondary complication of fungal pneumonia, is widely considered to have an increasing incidence and high mortality. Itraconazole (Itz) can inhibit ergosterol biosynthesis to treat pulmonary aspergillosis. Nevereless, Itz’s clinical application is limited because of its poor water solubility, low oral bioavailability, and systemic hepatotoxicity. In this study, Itz-loaded nanostructured lipid carriers (Itz-NLCs) were developed to improve the in vitro permeability and bioavailability of Itz via pulmonary administration.Methods Itz-NLCs were prepared by the emulsification-evaporation method using oleic acid and glycerol monostearate as liquid and solid lipids, respectively.Results The Itz-NLCs were optimized with tiny particle size, uniform distribution, and excellent entrapment efficiency (EE, 97.57% ± 0.45%). A Xenopus alveolar membrane was used in the permeation study, and the cumulative permeation percentage of Itz was 10% for Itz-NLCs at 8 h, which was 2.50-fold higher than that for Itz suspensions (4%, p < .001). A rabbit pharmacokinetic investigation revealed that Itz-NLCs have an 83.05% absolute bioavailability after intratracheal instillation.Conclusions The purpose of Itz-NLCs is to enhance the bioavailability and permeability of Itz in vitro for administration via the lungs.
研究领域:
药剂学
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医学真菌学
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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
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 3
·1-12
·
IF 3.3
Zhang Qian,Li Yongquan,Li Linghui,Cheng Yushan,Yu Fangkun,Li Rui,Hou Shuguang
Amorphous and crystalline active pharmaceutical ingredients (APIs) are both widely studied for pulmonary delivery. The past research mainly studied the impact of solid-state properties on pharmacokinetic attributes; however, the influence of solid-state properties on aerosolization performance was much less studied. This study aimed to investigate the different aerosolization performances of amorphous and crystalline curcumin (Cur) stabilized with L-leucine. Cur was spray-dried with different concentrations of L-leucine (0, 5, 20, 35, and 50%, w/w) as both solution-based and suspension-based formulations to acquire amorphous and crystalline Cur powders. The physicochemical properties of the spray-dried powders, including particle size, morphology, and solid-state characteristics, were studied. The aerosolization performance as well as dissolution properties were evaluated. It was found that 35% (w/w) L-leucine or above led to the formation of amorphous Cur in the spray-dried powders, and the amorphous Cur powders exhibited higher FPF (70.8%, with 50% L-leucine, w/w) than the crystalline Cur formulations with an FPF at 56.3% (with 50% L-leucine, w/w). In conclusion, with a high concentration of L-leucine (35% or above) in the formulations, amorphous Cur would exhibit higher aerosolization efficiency than crystalline Cur. However, with a low concentration of L-leucine (20% or less) in the formulations, crystalline Cur would be preferred for more enhanced consideration. Graphical Abstract
研究领域:
药学
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肺科学
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制剂科学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 3.616
Xichun Qin,Yeqing Zhou,Yuzhuo Wang,Ziyao Wang,Yun Wang,Jiali Chen,Lidong Zhu,Xiaoyu Quan,Zhiwei Liu,Hao Zhang,Liqun Jiang,Hongyan Dong,Zhongming Zhang
In the treatment of heart disease, strategies for the targeted delivery of protein therapeutics to the heart by inhalation are still immature. Perfluorocarbons (PFCs) are inert chemicals with good biocompatibility , and unique physico-chemical properties that have recently led to their applications in numerous fields. In this study, we combined the advantages of protein-phospholipid complexes and PFC emulsions and then synthesized protein-loaded PFC nanoemulsions (PNEs) to test whether, after inhalation, these nanoemulsions could deliver therapeutic proteins to the heart. After preparing protein-phospholipid complexes by lyophilization, we obtained PNEs by extrusion. The particle size and surface charge of PNEs were about 140 nm and -50 mV, respectively. In vitro results showed that the PNEs had a fine particle fraction of 35% and exhibited sustained protein release. Translocation studies were done using three types of pulmonary epithelial cells, and ~7% translocation was observed in the Calu-3 cell line. Further, they were easily absorbed by cells and had therapeutic effects in culture. In vivo results showed that the PNEs successfully delivered proteins to the myocardial tissue of rats and reduced ischemic myocardial injury caused by acute myocardial infarction (AMI). This study suggests that inhalation of PNEs is a new potential strategy to deliver proteins to cardiac tissues for treating heart diseases.
研究领域:
药学
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纳米技术
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心脏病学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Wenhua Wang,Wenhao Wang,Shiwei Jin,Fangqin Fu,Zhengwei Huang,Ying Huang,Chuanbin Wu,Xin Pan
Cisplatin (DDP)-based ferroptosis-apoptosis synergetic therapy is a novel strategy of lung cancer treatment based on the targeted induction of high oxidative stress levels in tumor cells. Nevertheless, the strong antioxidant system in tumor cells and low accumulation at the lesion site result in its low sensitivity as well as systemic side effects. To circumvent the strong antioxidant system, the combination of Reactive Oxygen Species (ROS) generator DDP and a glutathione (GSH) scavenger β-Phenethyl isothiocyanate (PEITC) was a potential strategy. Besides, pulmonary delivery equipped with lung tumor targeting nanoformulations was expected to promote tumor lesions accumulation. Herein, an inhalable core–shell nanocomposite, PEITC-loaded solid lipid nanocores coated with DDP-encapsulated hyaluronic acid (HA) shell (PNDH) based on the strategy of “open pocket and tighten holes” was developed. The nicotinamide adenine dinucleotide phosphate oxidases 4 (NOX4) was upregulated by DDP to “open pocket for ROS” while the PEITC could deplete the GSH to “tighten holes”, preventing ROS consumption. Upon nebulization, improved lung drug accumulation with about 6.7 times higher than intravenous injection and excellent lung retention was exhibited. Equipped with tumor membrane CD44 targeted HA, the tumor recognizing efficiency was elevated about two times. The remarkably enhanced tumor inhibition effect was revealed both in vitro and in vivo, and the PNDH-driven cell damage process was described as a result of mitochondrial dysfunction and osmotic pressure mediated cell membrane broken. Taken together, the rationally designed PNDH enhanced the effectiveness of ferroptosis-apoptosis synergetic therapy by the “open pocket and tighten holes” strategy.
研究领域:
肿瘤学
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药学
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纳米技术
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治疗学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Jinxue Cao,Yaping Xiu,Siqi Wang,Fangling Wu,Ji Li,Dongkai Wang
Andrographolide (AG) is known as a "natural antibiotic". It has been clinically developed into capsules, dropping pills, disperse tablets, etc., for the treatment of viral and bacterial upper respiratory tract infections. It has poor water solubility, obvious P-glycoprotein efflux, and low bioavailability, so its wide application in clinical practice is limited. In this work, a novel AG dry powder inhaler (AG-DPI) was developed using experimental design to optimize the prescription and spray-drying process to obtain higher local concentrations in the lungs while lowering the administered dose; avoiding hepatic first-pass effects and gastrointestinal p-glycoprotein efflux. The short-term local anti-inflammatory effects in the lungs were evaluated using a rat model of acute pneumonia compared with oral administration. The prepared AG-DPI showed that (1) it had good aerosolization properties and was suitable for pulmonary administration, with emitted doses >90%, and fine particle fractions >60%; (2) it was superior to oral administration in the assessment of local anti-inflammatory effects in the lungs by acting on acute pneumonia. This study provides some theoretical value and reference for the inhalable dry powder of AG as a potential targeted treatment modality for lung diseases and infections.
研究领域:
药剂学
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药理学
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呼吸病学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Photodiagnosis and Photodynamic Therapy
·
2020
·
IF 2.894
Tongtong Zhang,Jianwei Bao,Mengmeng Zhang,Yuanyuan Ge,Jianming Wei,Yu Li,Weixia Wang,Miao Li,Yiguang Jin
Lung cancer is a severe disease with high mortality. Chemotherapy is one major treatment for lung cancer. However, systemic chemotherapeutics usually distribute throughout the body without specific lung distribution so that serious side effects are unavoidable. Photodynamic therapy (PDT) is occasionally used for lung cancer treatment but photosensitizers are also systemically administered and the bronchoscopic intervention under anesthesia may hurt lung tissues. Here, we combined inhaled chemotherapeutics and photosensitizers for chemo-photodynamic therapy (CPDT) of primary lung cancer of rats with external laser light irradiation. Gefitinib PLGA nanoparticles (GNPs) were prepared. The anti-cancer effects of GNPs and/or a common photosensitizer 5-aminolevulinic acid (5-ALA) were explored on A549 cells (adenocarcinomic human alveolar basal epithelial cells) and primary lung cancer rats after intratracheal administration. External light irradiation was applied due to its higher safety compared to internal light irradiation that may result in injuries after a laser optic fiber was intubated into the lung. The remarkable synergistic effect of CPDT was confirmed although the single therapies were also effective, where the high anti-lung cancer effects were shown and some typical lung cancer markers, including CD31, VEGF, NF-κB p65 and Bcl-2, significantly decreased. Moreover, the treatments attenuated inflammation with the downregulation of TNF-α. The combination of pulmonary drug delivery and chemo-photodynamic therapy is a promising strategy for treatment of lung cancer.
研究领域:
肿瘤学
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药学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
ULTRASONICS SONOCHEMISTRY
·
2025
·
IF 9.7
Yan Zhao,Kai Feng,Boxin Liu,Zhihao Zhang,Haozhou Huang,Mateng Chen,Qingzhen Zhang,Gang Yang,Mengxing Lin,Yulong Zhang,Hanhan Li,Ning Xue,Kaiqi Shi,Qiang Da,Bin Dong
Aspirin is an antiplatelet agglutinating drug used clinically for the prevention and treatment of angina pectoris, myocardial infarction, and cerebral thrombosis. In this study, aspirin inhalable powder was prepared by ultrasound-intensified anti-solvent crystallization (UIAC) and developed for rapid antiplatelet aggregation, which could reduce the dose and gastrointestinal irritation. The particle size distribution, morphology, density, fluidity, and in vitro aerodynamic performance of the as-prepared powders were systematically evaluated. Meanwhile, machine learning methodology, specifically utilizing the Decision Tree Regressor in conjunction with Shapley Value analysis, was applied to elucidate the influence of critical process parameters within the production process. The powder flowability could be improved by the addition of excipients L150 and L-leucine (Leu). The value of fine particle fraction (FPF) increased from 10.40 % to 45.86 % when adding L150 (60 %, w/w) and Leu (5 %, w/w). The cytotoxicity study of aspirin inhalable powder was performed at cellular level, and demonstrated aspirin powder had no significant toxic effect. The Calu-3 cell monolayer interfaced to simulate lung epithelial tissue, demonstrated the high permeability of inhalable powder in lung. Pharmacokinetics were investigated in healthy rats, compared with oral administration, the T max of inhale administration (10 min) was significantly shorter than oral administration (30 min), and the AUC was 1.91 times higher than that of the oral administration, demonstrating that pulmonary drug delivery accelerated the absorption and increased the bioavailability of aspirin.
研究领域:
药学
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药物递送
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生物医学工程
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晶体工程
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机器学习
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毒理学
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药代动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2021
·
IF 11.614
Ting Chen,Bo Zhuang,Yueqi Huang,Yan Liu,Bochuan Yuan,Wanmei Wang,Tianyu Yuan,Lina Du,Yiguang Jin
Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ -ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ -ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60 Co γ -ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.
研究领域:
放射肿瘤学
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纳米技术
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药剂学
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肺科学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Lan Wu,Lin-Ping Wu,Jingya Wu,Jin Sun,Zhonggui He,Cristina Rodríguez-Rodríguez,Katayoun Saatchi,Lea Ann Dailey,Urs O. Häfeli,Dongmei Cun,Mingshi Yang
Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid–polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.
研究领域:
药剂学
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纳米技术
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分子生物学
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肺科学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2015
·
IF 2.023
Liandong Hu,Saixi Pang,Qiaofeng Hu,Deliang Gu,Dongqian Kong,Xiaoyun Xiong,Jianying Su
Background The current study aimed to investigate whether the novel folate (FT) modified nanoparticles (NPs) co-loaded with docetaxel (DT) and curcumin (CU) (named as FT-NPs) could enhance the delivery efficiency to tumor compared with the NPs without FT (non-targeted NPs). Methods FT-NPs were successfully formulated in this article. In vitro cytotoxic activity against A549 cells and in vivo antitumor activity of FT-NPs in S180 cell bearing mice were conducted. Cellular uptake test was used to evaluate uptake efficiency of FT-NPs. Histological observation was used to determine the lung security. Besides, the physical chemical properties such as stability, particle size, zeta potential , drug encapsulation efficiency, transmission electron microscopy (TEM) were also conducted. Results FT-NPs exhibited stronger growth inhibition effects on A549 cells compared with non-targeted NPs, moreover, the novel FT-NPs indicated more effective antitumor efficacy in inhibiting tumor growth. Confocal laser scanning microscopy indicated that the uptake of FT-NPs was facilitated and effective. Histological observation meant that FT-NPs were biocompatible and appropriate for pulmonary administration. Conclusion These results confirmed that FT-NPs with relatively high drug loading capacity could effectively inhibit tumor growth and reduce toxicity. The novel FT-NPs could produce as an outstanding nanocarrier for the targeted treatment of cancers .
研究领域:
药学
·
纳米技术
·
肿瘤学
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生物医学工程
✓ 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）