DRUG DELIVERY
·
2016
·
IF 4.843
Wenping Wang,Yaqin Cai,Guangxing Zhang,Yanhua Liu,Hong Sui,Kinam Park,Hong Wang
Lung-targeting sophoridine-loaded poly(lactide-co-glycolide) (PLGA) microspheres were constructed by a simple oil-in-oil emulsion-solvent evaporation method. The obtained microspheres were systematically studied on their morphology, size distribution, drug loading, encapsulation efficiency, in vitro release profile, and biodistribution in rats. The drug-loaded microparticles showed as tiny spheres under SEM and had an average size of 17 μm with 90% of the microspheres ranging from 12 to 24 μm. The drug loading and encapsulation efficiency were 65% and 6.5%, respectively. The in vitro drug release behavior of microspheres exhibited an initial burst of 16.6% at 4 h and a sustained-release period of 14 days. Drug concentration in lung tissue of rats was 220.10 μg/g for microspheres and 6.77 μg/g for solution after intraveneous injection for 30 min, respectively. And the microsphere formulation showed a significantly higher drug level in lung tissue than in other major organs and blood samples for 12 days. These results demonstrated that the obtained PLGA microspheres could potentially improve the treatment efficacy of sophoridine against lung cancer.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Ting Wu,Weiping Liao,Wei Wang,Jie Zhou,Weiguo Tan,Weibing Xiang,Jinglin Zhang,Lina Guo,Tao Chen,Dong Ma,Weiye Yu,Xiang Cai
Lung-targeted genipin-crosslinked deacetylated chitosan (GEN-CS)/isoniazid (INH)/rifampin (RMP) nanogel particles (NGPs) were prepared as a treatment for tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB) to surmount the undesirable side effects and decrease the cytotoxicity of INH and RMP when being against MTB. The size, morphology, in vitro release property, long-term antibacterial performance, stability, in vitro cytotoxicity, in vivo toxicity, and in vivo release property of GEN-CS/INH/RMP NGPs inhalation powder were investigated. The results showed that the GEN-CS/INH/RMP NGPs inhalation powder exhibited extended antibacterial activity because of its long-term release of INH and RMP. A simplex GEN-CS/INH/RMP NGPs pulmonary dose led to the therapeutic drug concentration of 40%–60% in lung and other organs (＜5%) for 24 h. Furthermore, this GEN-CS/INH/RMP NGPs lyophilized inhalation powder displayed lung-targeted property and lower in vivo toxicity. These results suggested that this GEN-CS/INH/RMP NGPs inhalation powder would be a more useful dosage form than separate dose of INH or RMP for MTB.
研究领域:
药剂学
·
结核病治疗
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Jieqiong Lv,Runcheng Liang,Zihua Xia,Yong Li,Zhufen Lv,Dongzhi Hou,Liping Yu,Gang Chen,Yi Liu,Fan Yang
Purpose: A series of β-CD amphiphilic star-shaped copolymers with exceptional characteristics were synthesized and their potential as carriers for micelles drug delivery was investigated.Methods: A series of amphiphilic copolymers based on β-CD were synthesized by introducing poly (acrylic acid)-co-poly(methyl methacrylate)-poly (vinyl pyrrolidone) or poly (acrylic acid)-co-poly(methyl methacrylate)-co-poly(monoacylated-β-CD)-poly (vinyl pyrrolidone) blocks to the primary hydroxyl group positions of β-CD. The micellization behavior of the copolymers, the synthesis conditions, characteristics, drug release in vitro and tissue distribution of vinpocetine (VP) micelles in vivo were investigated.Results: Around 60 types of β-CD amphiphilic star-shaped copolymers were successfully synthesized and the critical micelle concentration ranged from 9.80 × 10−4 to 5.24 × 10−2g/L. The particle size, drug loading and entrapment efficiency of VP-loaded β-CD-P4 micelles prepared with optimal formulation were about 65 nm, 21.44 ± 0.14%, and 49.05 ± 0.36%, respectively. The particles had good sphericity. The cumulative release rates at 72 h of VP-loaded β-CD-P4 micelles in pH 1.0, pH 4.5, pH 6.5, or pH 7.4 media were 93%, 69%, 49%, and 43%, respectively. And, the lung targeting efficiency of VP-loaded β-CD-P4 micelles was 8.98 times higher than that of VP injection.Conclusion: The VP-loaded β-CD-P4 micelles exhibited controlled-release property, pH-induced feature and lung targeting capacity compared with VP injection, suggesting that the β-CD-P4 copolymers are an excellent candidate for micelles drug delivery.
研究领域:
药剂学
·
生物材料
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Jing Tang,Jianming Li,Guo Li,Haitao Zhang,Ling Wang,Dai Li,Jinsong Ding
Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic-co-glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung. Spd-AKF-PLGA NPs were prepared and functionalized by modified solvent evaporation with Spd and polyethylene glycol (PEG)-PLGA groups. The size of Spd-AKF-PLGA NPs was 172.5±4.3 nm. AKF release from NPs was shown to fit the Higuchi model. A549 cellular uptake of an Spd–coumarin (Cou)-6-PLGA NP group was found to be almost twice as high as that of the Cou-6-PLGA NP group. Free Spd and difluoromethylornithine (DFMO) were preincubated in A549 cells to prove uptake of Spd-Cou-6-PLGA NPs via a polyamine-transport system. As a result, the uptake of Spd-Cou-6-PLGA NPs significantly decreased with increased Spd concentrations in incubation. At higher Spd concentrations of 50 and 500 µM, uptake of Spd-Cou-6-PLGA NPs reduced 0.34- and 0.49-fold from that without Spd pretreatment. After pretreatment with DFMO for 36 hours, cellular uptake of Spd-Cou-6-PLGA NPs reached 1.26-fold compared to the untreated DFMO group. In a biodistribution study, the drug-targeting index of Spd-AKF-PLGA NPs in the lung was 3.62- and 4.66-fold that of AKF-PLGA NPs and AKF solution, respectively. This suggested that Spd-AKF-PLGA NPs accumulated effectively in the lung. Lung-histopathology changes and collagen deposition were observed by H&E staining and Masson staining in an efficacy study. In the Spd-AKF-PLGA NP group, damage was further improved compared to the AKF-PLGA NP group and AKF-solution group. The results indicated that Spd-AKF-PLGA NPs are able to be effective nanocarriers for anti–pulmonary fibrosis therapy.
研究领域:
药学
·
肺病学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Chemistry
·
2025
·
IF 9.7
Zhang Wen,Li Jiaxin,Wang Nan,Li Muzi,Peng Chen,Zhang Xinyue,Ouyang Guanghui,Li Yan
Lipid nanoparticles (LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment. Although LNPs are particularly advantageous for in vivo delivery, the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging. To address this issue, we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine) (PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA (siRNA). Three libraries with 90 PMPC-LNPs@siRNA were established. The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about 90%. The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin, mediating lung-targeted delivery of siRNA. With good cellular uptake and endo/lysosomal escape ability, in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α (TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels, and improved the pathological features of lung inflammation. Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation. Therefore, this work offered a promising siRNA therapeutic approach for lung diseases.
研究领域:
药学
·
纳米技术
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2021
·
IF 20.722
Hongyang Yu,Bing Wang,Shuang Zhou,Meilin Zhu,Wei Chen,Hanqing Chen,Xue Li,Shanshan Liang,Meng Wang,Lingna Zheng,Lina Zhao,Zhifang Chai,Weiyue Feng
Nanomaterials (NMs) as lung-targeted drug delivery vehicles have attracted great attentions. Recent studies indicated that elastic or deformable property of NMs could play a vital role in biomedical applications . Herein, polyvinylpyrrolidone (PVP) functionalized graphene oxide (GO-PVP) via a facile one-pot method and PEGylated GO (GO-PEG) nanosheets (NSs) were synthesized at room temperature . By using rare earth elemental labeling method, we quantitatively revealed that GO-PVP NSs were targeting retention in the lung that after 4 h intravenous injection, the lung/liver and lung/spleen ratios in GO-PVP treated mice were about 230-fold and 30-fold higher of those in GO-PEG treated mice, respectively, especially a considerable amount was retained in the lower respiratory tract including pulmonary interstitium and alveolar region as fibril-like shapes. The florescence imaging and in situ confocal Raman microscopy combining with laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) elemental imaging analysis further confirmed that a more amount of GO-PVP than GO-PEG retention in the pulmonary interstitium. Utilizing atomic force microscopy PeakForce quantitative nanomechanical mapping technique, the nanomechanical property investigation shows that GO-PVP NSs are softer, more adhesive and deformable than GO-PEG NSs. Further, the molecular dynamics simulations illustrate that GO-PVP has deformable structure due to the hydrogen-bond interaction at basal plane between PVP and GO that cause GO-PVP surface roughness and to possess low solvent accessible surface area (SASA), comparatively, the GO-PEG owns relatively firm structure and higher SASA. This study indicates that the well dispersion property and deformable structure of GO-PVP in the lung contribute to its filtration of the endothelial/epithelial barrier and retention in the interstitium and alveolar region. Importantly, the study inspires us to design elastic or deformable NMs in response to the lung disease especially those have occurred in the lower respiratory tract.
研究领域:
纳米技术
·
生物医学工程
·
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Feiyang Jin,Di Liu,Hui Yu,Jing Qi,Yuchan You,Xiaoling Xu,Xuqi Kang,Xiaojuan Wang,Kongjun Lu,Xiaoying Ying,Jian You,Yongzhong Du,Jiansong Ji
Acute lung injury (ALI) is a serious illness without resultful therapeutic methods commonly. Recent studies indicate the importance of oxidative stress in the occurrence and development of ALI, and mitochondria targeted antioxidant has become a difficult and hot topic in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted microsphere (MS) for ALI therapy are developed, with triphenylphosphonium cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically target the mitochondria, increasing the effect of antioxidant. The results manifest that with the increase of microsphere, lung distribution of microsphere is also increased in murine mice, and after SA modification, the microsphere exhibits the ideal lung-targeted characteristic in ALI model mice, due to SA efficiently targeting to E-selectin expressed on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS has better antioxidative capacity, decreases intracellular ROS generation, and increases mitochondrial membrane potential, contributing to a lower apoptosis rate in human umbilical vein endothelial cells (HUVECs) compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has been alleviated markedly and the oxidative stress is ameliorated efficiently. Significant histological improvements by SA/Cur-TPP/MS are further proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a promising drug formulation for ALI therapy.
研究领域:
药学
·
生物医学工程
·
药理学
·
治疗学
·
药物递送系统
·
肺疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2021
·Vol. 12
·期 5
·1080-1095
·
IF 4.617
Su Meiling,Hu Heping,Zhao Xuan,Huang Chengyuan,Yang Bowen,Yin Zongning
This study evaluated the D-mannose modified polyethyleneimine-block-polycaprolactone biomacromolecule copolymer micelles (PCL-PEI-mannose) as a targeted delivery of the glucocorticoid dexamethasone (DXM) to lung inflammation tissues and enhances the vehicle for its anti-inflammatory effects. Dexamethasone was encapsulated in the hydrophobic core of cationic polymer micelles by solvent evaporation. The polymeric micelles exhibited sustained-release within 48 h, good blood compatibility, and colloidal stability in vitro. The cellular uptake of mannose-modified micelles was higher compared with the non-modified micelles. And drug-loaded targeted micelles could inhibit the production of inflammatory factors in activated RAW264.7 cells. The distribution results indicated that drug-loaded targeted micelles highly improved the lung targeting ability, reduced the wet/dry ratio of injured lung tissue, and relieved the lung inflammation, accompanied by the decrease of inflammatory cell infiltration, myeloperoxidase activity, and inflammatory mediator levels in bronchoalveolar lavage fluid. These findings suggested that PCL-PEI-mannose delivery system could facilitate the lung-specific delivery and inhibit the inflammatory response. Collectively, PCL-PEI-mannose polymer micelles could be used as a potential delivery system for the treatment of acute lung injury (ALI). Graphical abstract
研究领域:
药学
·
纳米技术
·
生物医学工程
·
炎症研究
·
药物递送系统
✓ 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）