INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
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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
·
生物化学
✓ 已验证
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
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Zhengwei Huang,Ying Huang,Cheng Ma,Xiangyu Ma,Xuejuan Zhang,Ling Lin,Ziyu Zhao,Xin Pan,Chuanbin Wu
The objective of this study was to perform the in vitro and in vivo validation of an endotracheal aerosolization (ETA) device (HRH MAG-4, HM). Solid lipid nanoparticle suspension (SLNS) formulations with particle sizes of approximately 120, 240, 360, and 480 nm were selected as model nanoparticle suspensions for the validation. The emission rate (ER) of the in vitro aerosolization and the influence of aerosolization on the physicochemical properties were investigated. A high ER of up to 90% was obtained, and no significant alterations in physicochemical properties were observed after the aerosolization. The pulmonary deposition of model drug budesonide in Sprague–Dawley rats was determined to be approximately 80%, which was satisfactory for pulmonary delivery. Additionally, a fluorescent probe with aggregation-caused quenching property was encapsulated in SLNS formulations for in vivo bioimaging, after excluding the effect of aerosolization on its fluorescence spectrum. It was verified that SLNS formulations were deposited in the lung region. The results demonstrated the feasibility and reliability of the HM device for ETA in laboratory investigation.
研究领域:
药剂学
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生物医学工程
·
呼吸系统研究
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Xu Zuo,Yinuo Gu,Xiaoping Guo,Wenxue Zheng,Haoyu Zheng,Yiming An,Caina Xu,Fang Wang
Purpose Inhaled corticosteroids, including budesonide (BUD), are widely employed for the treatment of asthma. However, the frequent use of corticosteroids is associated with numerous adverse effects and poses challenges to ongoing drug therapy and patient adherence. Budesonide liposomal nanoparticles (BUD-LNPs) were developed to improve the bioavailability of the drug and thereby improve the effectiveness of asthma treatment.Methods BUD-LNPs were prepared via thin-film hydration, and the characterizations, stability, and in vitro release of BUD-LNPs were studied. In vitro cellular uptake was observed by laser-scanning confocal microscope (LSCM) and flow cytometry. And the in vitro anti-inflammatory activity of BUD-LNPs was evaluated by measuring the expression of pro-inflammatory cytokines in activated macrophages. Besides, the accumulation time in the lung of drugs delivered via liposomal carriers and free drugs was compared in vivo. And the in vivo therapeutic efficacy of BUD-LNPs was assessed in OVA-induced asthmatic mice. Finally, in vivo biosafety assessment was performed.Results The particle size, PDI, and zeta potential of BUD-LNPs were 127.63±1.33 nm, 0.27±0.02, and 3.33±0.13 mV, respectively. BUD-LNPs exhibited excellent biosafety and anti-inflammatory activity in vitro. Furthermore, compared with the free drugs, the utilization of liposomal nano-vehicles for drugs delivery could effectively extend the duration of drugs accumulation in the pulmonary system. Additionally, treatment with BUD-LNPs alleviated airway hyperresponsiveness, reduced airway mucus secretion, and mitigated pulmonary inflammation in OVA-induced asthmatic mice. And the BUD-LNPs demonstrated superior therapeutic efficacy compared to free BUD.Conclusion BUD-LNPs was successfully prepared with excellent stability and sustained release for 24 h in vitro. The data of anti-inflammatory activity, asthma therapeutic effects and safety studies indicated that drug delivery mediated by liposomal nano-vehicles was a feasible and desirable strategy for medical strategy and showed great promise in the clinical therapy of asthma.
研究领域:
药剂学
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药理学
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纳米技术
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呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2017
·
IF 4.811
Suhui Ni,Yun Liu,Yue Tang,Jing Chen,Shuhan Li,Ji Pu,Lidong Han
The effect of gene silencing by survivin siRNA (siSurvivin) on the proliferation and apoptosis of lung tumor has been attracted more interest. GABA B receptor ligand-directed nanoparticles consisting of baclofen functionalized trimethyl chitosan (Bac-TMC) as polymeric carriers, tripolyphosphate (TPP) as ionic crosslinker, and siSurvivin as therapeutic genes, were designed to enhance the survivin gene silencing. GABA B receptor agonist baclofen (Bac) was initially introduced into TMC as a novel ligand. This Bac-TMC/TPP nanoparticles increased the uptake of survivin siRNA through the interaction with GABA B receptor, further resulted in efficient cell apoptosis and gene silencing. For siRNA-loaded nanoparticles pulmonary delivery, mannitol was utilized for it delivery into pressurized metered dose inhalers (pMDI). The fine particle fractions of this formulation was (45.39 ± 2.99)% indicating the appropriate deep lung deposition. These results revealed that this pMDI formulation containing Bac-TMC/TPP nanoparticles would be a promising siRNA delivery system for lung cancer treatment.
研究领域:
药学科学
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纳米技术
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分子生物学
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药物递送系统
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2023
·
IF 4.9
Dongli Qi,Bei Jia,Hui Peng,Jiachen He,Jiaxin Pi,Pan Guo,Ying Zhang,Xiuping Deng,Jiawei Li,Zhidong Liu
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal lung disease caused by multiple factors. Currently, safe, and effective drugs for the treatment of IPF have been extremely scarce. Baicalin (BA) is used to treat pulmonary fibrosis, IPF, chronic obstructive pulmonary disease, and other lung diseases. Ambroxol hydrochloride (AH), a respiratory tract lubricant and expectorant, is often used to treat chronic respiratory diseases, such as bronchial asthma, emphysema, tuberculosis, and cough. The combination of BA and AH can relieve cough and phlegm, improve lung function, and potentially treat IPF and its symptoms. However, given the extremely low solubility of BA, its bioavailability for oral absorptions is also low. AH, on the other hand, has been associated with certain side effects, such as gastrointestinal tract and acute allergic reactions, which limit its applicability. Therefore, an efficient drug delivery system is urgently needed to address the mentioned problems. This study combined BA and AH as model drugs with L-leucine (L-leu) as the excipient to prepare BA/AH dry powder inhalations (BA/AH DPIs) using the co-spray drying method. We the performed modern pharmaceutical evaluation, which includes particle size, differential scanning calorimetry analysis, X-ray diffraction, scanning electron microscope, hygroscopicity, in vitro aerodynamic analysis, pharmacokinetics, and pharmacodynamics. Notably, BA/AH DPIs were found to be advantageous over BA and AH in treating IPF and had better efficacy in improving lung function than did the positive drug pirfenidone. The BA/AH DPI is a promising preparation for the treatment of IPF given its lung targeting, rapid efficacy, and high lung bioavailability.
研究领域:
药剂学
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肺病学
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药物递送系统
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Mengqi Tong,Xi Kuang,Qiaoying Jiang,Gaoxiang Li,Lulu Jin,Yihao Ye,Yi Pan,Yang Zhu,Xiaozhou Mou,Zhengwei Mao,Yueliang Zheng
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.
研究领域:
药剂学
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生物医学工程
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呼吸医学
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生物材料
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Zhimei Xiao,Bo Zhuang,Guoli Zhang,Miao Li,Yiguang Jin
Sonodynamic therapy (SDT) has been tried for cancer treatment; however, sonosensitizers are usually administered by injection, leading to low distribution in the tumor tissue and compromised therapeutic effect, even serious side effect. Here, we combined cationic liposomal hydroxycamptothecin (CLH) and 5-aminolevulinic acid (5-ALA) via intratracheal (i.t.) administration for the chemo-sonodynamic (Chemo-SDT) therapy of metastatic lung cancer. CLH was prepared from HCPT and the lipid mixture of soybean lecithin/cholesterol/octadecylamine with a film method. The optimal pre-incubation time of 5-ALA with tumor cells before ultrasound exposure was 4 h, for sake of sonosensitizer accumulation, i.e., protoporphyrin IX, the metabolite of 5-ALA. In vitro studies showed the higher cytotoxicity of Chemo-SDT compared to the other treatments, including i.t. CLH, intravenous (i.v.) CLH, and SDT alone. The combination of pulmonary delivery and Chemo-SDT showed the highest anticancer effect among the treatments on the metastatic lung tumor-bearing mice, which was judged according to the tumor appearance and pathological sections. The major anticancer mechanism of Chemo-SDT included the improved apoptosis of cancer cells and the enhanced production of reactive oxygen species, and more importantly, the synergy of chemotherapy and SDT. Pulmonary delivery of chemotherapeutics and sonosensitizers is a promising strategy for the treatment of lung cancer.
研究领域:
肿瘤学
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药剂学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Mingyuan Li,Xianglong Wang,Mengsi Yin,Faxin Zhang,Wenlin Ma,Linze Che,Jinhao Yu,Yan Cheng,Mengju Xu,Xiaofu Liang,Wen Su,Hongmeng Ren,Weixue Si,Jingsi Ma,Shaodan Peng,Xiaolong Zhao,Jiaping Zhou,Ziqi Wu,Jiang Deng,Hua Sun
Lung cancer is the most prevalent and deadly tumor globally, marked by drug resistance and a poor prognosis. Specialized formulations with strong lung targeting are currently lacking. Docetaxel (DTX) and TUBB3-siRNA represent chemotherapy and RNA interference (RNAi), two strategies for lung cancer treatment. Lipid nanoparticles (LNPs) are nanocarriers suitable for nucleic acid delivery. In this study, spray freeze-drying (SFD) converted LNP colloidal solutions into inhalable dry powders. Fresh and rehydrated LNP (SFD) showed sizes below 200 nm, ζ potentials near 0 mV, and uniform roundness by transmission electron microscopy. The geometric particle size distribution (D50) of TUBB3-LNPs, DTX-LNPs, and TUBB3/DTX-LNPs inhalable powders did not differ significantly (1.99–5.90 μm). The median mass aerodynamic diameter (MMAD) was 2.61 ± 0.32 μm, suitable for pulmonary deposition. Experiments with BEAS-2B and H460 cells showed that TUBB3/DTX-LNPs had low cytotoxicity and good biocompatibility with BEAS-2B but strongly inhibited H460 cells. Differences in apoptosis induced by fresh LNPs and rehydrated LNP (SFD) indicate that the SFD process preserves normal cell viability while maintaining tumor inhibition. Because dry powder inhalers combine the drug formulation with the delivery device, a specialized single-dose prefilled device was developed that featured four symmetrically configured orifices (vents) located in the middle of the tube body; it achieved a high dry powder emptying rate of 95–100%. Furthermore, this study demonstrated the lung-targeting efficacy and sustained-release properties of the formulation.
研究领域:
药剂学
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纳米技术
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肿瘤学
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药物递送
·
呼吸医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Bei Jia,Jiachen He,Ying Zhang,Wenli Dang,Bin Xing,Mengru Yang,Haonan Xie,Jiawei Li,Zhidong Liu
Chronic obstructive pulmonary disease (COPD) is a prevalent lung condition characterized by airflow obstruction, disability, and high mortality rates. Magnolol (MA), known for its anti-inflammatory and antioxidant properties, holds the potential for alleviating COPD symptoms. However, MA faces challenges like poor aqueous solubility and low bioavailability. Herein MA-loaded nanostructured lipid carriers (MA-NLC) were prepared using emulsification and solvent evaporation. These carriers exhibited a particle size of (19.67 ± 0.36) nm, a polydispersity index of (0.21 ± 0.01), and a zeta potential of (−5.18 ± 0.69) mV. The fine particle fraction of MA-NLC was (68.90 ± 0.07)%, indicating minimal lung irritation and enhanced safety. Pulmonary delivery of MA-NLC via nebulizer actively targeted the diseased lung tissues, facilitated slow release, and overcame the challenges of low oral absorption and bioavailability associated with MA. This formulation prolonged the residence time of MA and optimized its therapeutic effect in pulmonary tissues. Upon pulmonary administration, MA-NLC effectively regulated inflammatory and oxidative stress markers in COPD models, demonstrating its potential as a promising therapeutic platform for COPD management.
研究领域:
药学
·
肺科学
·
纳米技术
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 21
·2008960
·
IF 18.808
Jiandong Yang,Shanzhou Duan,Huan Ye,Chenglong Ge,Chunxian Piao,Yongbing Chen,Minhyung Lee,Lichen Yin
Pulmonary delivery of anti-inflammatory siRNA holds great potential in mitigating the cytokine storm during severe pneumonia. However, commonly utilized polycationic siRNA delivery vehicles can hardly penetrate the mucus barrier, thus greatly hurdling their therapeutic efficacy. Herein, TNF-α siRNA (siTNF-α) delivery nanocomplexes (NCs) are engineered with mucus/cytomembrane dual-penetration capabilities, realized via surface-coating of NCs with RC, an inflammation-sheddable, charge-reversal pro-peptide of RAGE-binding peptide (RBP). RC-coated dendritic poly- L -lysine/siTNF-α (DsT) NCs possess negative surface charges, and can thus efficiently penetrate the mucus layer after intratracheal administration. In the inflamed alveolar space with mild acidity, RC recovers to the cationic RBP and shed off, re-exposing the DsT NCs that efficiently transfect the alveolar macrophages and provokes TNF-α silencing. Thus, siTNF-α and RBP cooperatively alleviate the uncontrolled inflammation during acute lung injury. This study renders a unique approach for mediating trans-mucus nucleic acid delivery, and will find promising utilities for the treatment of severe pneumonia.
研究领域:
药剂学
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纳米技术
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肺科学
·
分子生物学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Di Ge,Siqi Ma,Tingting Sun,Yunfei Li,Jiaxing Wei,Chenao Wang,Xiaoyuan Chen,Yonghong Liao
Despite the recognized potential of inhaled nanomedicines to enhance and sustain local drug concentrations for lung cancer treatment, the influence of macrophage uptake on targeted nanoparticle delivery to and within tumors remains unclear. Here, we developed three ligand-coated nanoparticles for pulmonary delivery in lung cancer therapy: phenylboronic acid-modified nanoparticles (PBA-NPs), PBA combined with folic acid (FA-PBA-NPs), and PBA with mannose (MAN-PBA-NPs). In vitro, MAN-PBA-NPs were preferentially internalized by macrophages, whereas FA-PBA-NPs exhibited superior uptake by cancer cells compared to macrophages. Following intratracheal instillation into mice with orthotopic Lewis lung carcinoma tumors, all three nanoparticles showed similar lung retention. However, MAN-PBA-NPs were more prone to interception by lung macrophages, which limited their accumulation in tumor tissues. In contrast, both PBA-NPs and FA-PBA-NPs achieved comparable high tumor accumulation (∼11.3% of the dose). Furthermore, FA-PBA-NPs were internalized by ∼30% of cancer cells, significantly more than the 10–18% seen with PBA-NPs or MAN-PBA-NPs. Additionally, FA-PBA-NPs loaded with icaritin effectively inhibited the Wnt/β-catenin pathway, resulting in superior anti-tumor efficacy through targeted cancer cell delivery. Overall, FA-PBA-NPs demonstrated advantageous competitive uptake kinetics by cancer cells compared to macrophages, enhancing tumor targeting and therapeutic outcomes.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
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）