EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Li Chen,Chang-shun Liu,Qing-zhen Chen,Sen Wang,Yong-ai Xiong,Jing Jing,Jia-jia Lv
The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Chlorogenic acid (CA), an important bioactive compound from Lonicerae Japonicae Flos with poor permeability. SMEDDS was prepared and characterized by self-emulsifying rate, morphological observation, droplet size determination, stability, in vitro release, in vivo bioavailability and tissue distribution experiments. Results shown that the SMEDDS of CA has a high self-emulsifying rate (> 98%) in the dissolution media, and its microemulsion exhibits small droplet size (16.37 nm) and good stability. In vitro release test showed a complete release of CA from SMEDDS in 480 min. After oral administration in mice, significantly enhanced bioavailability of CA was achieved through SMEDDS (249.4% relative to the CA suspension). Interestingly, SMEDDS significantly changed the tissue distribution of CA and showed a better targeting property to the kidney (2.79 of the relative intake efficiency). It is suggested that SMEDDS improves the oral bioavailability of CA may mainly through increasing its absorption and slowing the metabolism of absorbed CA via changing its distribution from the liver to the kidney. In conclusion, it is indicated that SMEDDS is a promising carrier for the oral delivery of CA.
研究领域:
药剂学
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药物代谢动力学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2017
·Vol. 6
·期 1
·179-188
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IF 4.21
Jing Li,Cuiting Zhang,Weiming He,Hongzhi Qiao,Jiahui Chen,KaiKai Wang,David Oupický,Minjie Sun
Kidney-specific delivery is critically important for the treatment of renal fibrosis with drugs such as salvianolic acid B (Sal B). Here we report a kidney-specific nanocomplex formed by the coordination-driven assembly of catechol-modified low molecular weight chitosan (HCA-Chi), calcium ions and Sal B. The prepared HCA-Chi-Ca-Sal B (HChi-Ca-Sal B) nanocomplex reversed the TGF-β1-induced epithelial–mesenchymal transition (EMT) in HK-2 cells. In vivo imaging demonstrated a kidney-specific biodistribution of the nanocomplex. The anti-fibrosis effect of HChi-Ca-Sal B was tested in a mouse model of unilateral ureteral obstruction (UUO). Significant attenuation of the morphological lesions and the levels of extracellular matrix (ECM) proteins in the tubulointerstitium was observed in mice treated with HChi-Ca-Sal B, suggesting that the nanocomplex was able to prevent fibrosis better than the treatment with free Sal B. It was concluded that the HChi-Ca-Sal B nanocomplex showed a specific renal targeting capacity and could be utilized to enhance Sal B delivery for treating renal fibrosis.
研究领域:
药理学
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生物医学工程
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肾脏病学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 21
·7065-7075
·
IF 6.843
Xin Wang,Bingqing Deng,Meng Yu,Tao Zeng,Yuyu Chen,Jianqiang Hu,Qianqing Wu,Aiqing Li
Drug delivery nanoplatforms have been applied in bioimaging, medical diagnosis, drug delivery and medical therapy. However, insolubility, toxicity, instability, nonspecific targeting and short retention of many hydrophobic drugs limit their extensive applications. Herein, we have constructed a passive targeting and long retention therapeutic nanoplatform of core–shell gefitinib/poly (ethylene glycol)-polytyrosine nanocomplexes (Gef-PY NCs). The Gef-PY NCs have good water-solubility, non-toxicity (correspond to 1/10 dosage of effective gefitinib (hydrochloride) (Gef·HCl) (normal drug administration and slow-release) and high stability (120 days, 80% drug retention at 4 or 25 °C). The core–shell Gef-PY NCs present unexpected kidney targeting and drug slow-release capacity (ca. 72 h). The good water-solubility, non-toxicity and high stability of Gef-PY NCs effectively solve the bottleneck question that Gef-based therapy could be used only in intraperitoneal injection due to its insolubility and severe toxicity. Such excellent properties (e.g., water-solubility, non-toxicity, high stability, kidney targeting and long retention) of Gef-PY NCs create their prominent anti-fibrosis capabilities, such as decreasing approximately 40% tubulointerstitial fibrosis area and 68% expression of collagen I within 7 days. This therapeutic efficacy is well-matched with that of 10 times the dosage of toxic Gef·HCl. It is very hopeful that Gef-PY NCs could realize clinical applications and such a strategy offers an effective route to design high-efficiency treatments for kidney- and tumor-related diseases.
研究领域:
药学
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纳米技术
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治疗学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
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IF 4.5
Renxiang Yuan,Shuqian Yang,Ding Wang,Caini Yu,Peirong Li,Qi Jiang,Yangqian Luo,Tingting Meng,Fuqiang Hu,Tong Yu,Yupeng Liu,Hong Yuan
Ischemia-reperfusion (IR)-induced acute kidney injury (AKI) is a life-threatening form of AKI frequently observed in clinical settings, such as hemorrhagic shock, kidney transplantation, and cardiovascular surgery. Targeting renal antioxidant therapy may represent an effective strategy against IR-induced AKI. Bilirubin (BR), a specific superoxide anion scavenger, faces limitations in clinical application due to its poor water solubility and hepatic metabolism pathway. In this study, we prepared bilirubin nanocrystals (BRNCs), which demonstrated potent antioxidant effects in vitro experiments. To enhance renal targeting, BRNCs were encapsulated in poly(ethylene glycol) (PEG)-modified lipid nanoparticle (BRNC-LNP). In vivo distribution studies revealed that BRNC-LNP effectively circumvented hepatic metabolism and exhibited enhanced renal accumulation compared to BRNC. In vivo efficacy evaluation revealed superior therapeutic outcomes with BRNC-LNP versus BRNC in AKI mice. These findings suggest that BRNC-LNP may serve as a promising therapeutic strategy for IR-induced AKI by reducing the level of hepatic metabolism and promoting renal targeting.
研究领域:
纳米医学
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药剂学
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肾脏病学
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抗氧化治疗
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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
Small
·
2022
·Vol. 18
·期 48
·2204388
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IF 15.153
Jiajia Li,Qijia Duan,Xiaona Wei,Jianping Wu,Qiongqiong Yang
Acute kidney injury (AKI) is a common clinical disease with high morbidity and mortality, and with a lack of effective drugs for treatment. Oxidative stress is very important in the occurrence and progression of AKI, and antioxidants use is one of the promising treatments. Rosmarinic acid (RA) is a ubiquitous natural polyphenol with powerful antioxidant and anti-inflammatory activities. Due to its inherent characteristic with poor water solubility and inferior bioavailability, its clinical application is impeded. Hence, the authors design a nanoparticle for effectively delivering RA, which is a chemical complex of RA and fourth-generation poly-amidoamine-based amphiphilic polymer (G4-PAMAM). The nanoparticle is modified with l-serine due to the specific interaction between kidney injury molecule–1 (Kim-1) and serine, which eventually generates a promising AKI kidney–targeting nanoparticle (S-G-R). The S-G-R is rapidly cumulated and long-term retained in ischemia-reperfusion–induced AKI kidneys, especially in the damaged renal tubular cells. The S-G-R exhibits more excellent antioxidative and antiapoptotic effects in vitro and has a more outstanding ability to improve the renal function, repair damaged renal tissue, and decrease oxidative stress, inflammatory response and apoptosis of tubular cells in vivo. Overall, this study might develop a safe and effective targeting strategy for the therapy of AKI.
研究领域:
药学
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纳米技术
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肾脏生理学
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药理学
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产品关联
DOI
PubMed
高影响因子
Open Chemistry
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2020
·Vol. 18
·期 1
·1207-1216
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IF 1.216
Lishan Tan,Xiulong Deng,Xuandi Lai,Tao Zeng,Aiqing Li,Jianqiang Hu,Zuying Xiong
The aim of this study is to explore the kidney-targeting capability of mesoscale nanoparticles (MNPs)-emodin (Em-MNPs) and its potential antifibrosis in the animal model. First, MNPs and Em-MNPs were synthesized via nanoprecipitation method, and their diameters were both ∼400 nm with the uniform size. The entrapment efficiency of MNPs was 45.1% when adding emodin at the concentration of 12 mg/mL. Moreover, cytotoxicity assay showed that Em-MNPs presented excellent biocompatibility in rat proximal tubular cells. Cellular uptake assay demonstrated that Em-MNPs had high-efficiency uptake, especially in the cytoplasm. Ex vivo organ fluorescence imaging revealed that Em-MNPs possessed specific kidney-targeting ability with relative long retention time in the kidney (∼24 h). In the renal unilateral ureteral obstruction model, Em-MNPs treatment could significantly alleviate kidney tubule injury and reduce extracellular matrix deposition compared with free MNPs. Herein, Em-MNPs with specific kidney-targeting and preferable antifibrosis effects in animal model may pave an avenue for treating renal diseases.
研究领域:
药理学
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纳米技术
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肾病学
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产品关联
DOI
高影响因子
Materials Express
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2023
·Vol. 13
·期 12
·2092-2100
·
IF 0.7
Liu Qin
Renal injury, which is a prevalent condition, significantly impacts the health of competitive wrestlers. However, there is a limited number of therapeutic methods and drugs available for its treatment. To tackle this issue, a renal targeted drug based on functionalized polymer nanoparticles
(FPNPs) is being studied. The primary methods in the preparation of FPNPs involve utilizing the thin film hydration technique to create nanoparticles and encapsulating the drug TP within them as a treatment for renal injury, thus forming TP-FPNPs. Subsequently, the renal targeting of TP-FPNPs
is analyzed using in vitro organ fluorescence imaging techniques. Furthermore, a renal IRI model is constructed to assess the pharmacokinetics of TP-FPNPs using the application method. The preparation results of TP-FPNPs reveal a hydrated particle size of approximately 90 nm, which
remains in the renal region for over 48 hours. Additionally, the concentration content surpasses that of other organs by more than threefold after 12 hours. Moreover, in the application results, TP-FPNPs continue to possess a concentration of 302.5 ng/g even after 48 hours post-injection.
Based on the aforementioned results, it can be concluded that TP-FPNPs exhibit specific targeting, biocompatibility, and an extended retention time. Thus, this study is expected to effectively achieve the effect of treating renal injury in martial arts athletes, establishing an experimental
foundation for its clinical treatment.
研究领域:
纳米技术
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药学
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肾病学
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运动医学
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DOI
高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Ruixue Duan,Yueping Li,Ruru Zhang,Xuelan Hu,Yi wang,Jianfeng Zeng,Mingyuan Gao
Acute kidney injury (AKI) induced by ischemia reperfusion is closely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD + ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, we herein use an ultra-small Fe 3 O 4 nanoparticle as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD + . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe 3 O 4 nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD + precursor into renal cells through nicotinamide riboside kinase 1 on cell membrane. It was demonstrated that NMN-loaded Fe 3 O 4 nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicated that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previously strategies centering on anti-ROS (reactive oxygen species), anti-inflammation or even iron elimination. This article is protected by copyright. All rights reserved
研究领域:
肾病学
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药学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
·
IF 10.8
Zhiwei Huang,Changju Chun,Xinze Li
The management of acute kidney injury (AKI) imposes a significant medical burden. Due to the lack of effective drug transport vehicles, the administration of therapeutic agents for AKI cannot obtain the desired therapeutic effects. Kidney-targeted nanoparticles for renal delivery of drugs have shown promising potential as an emerging strategy for AKI therapy. However, these exogenous nanoparticles are rapidly cleared in the body and fail to achieve the expected renal targeting efficiency. Herein, we prepared the kidney targeting peptide-modified renal tubular epithelial cell membrane to coat zeolite imidazolate framework-8 nanoparticles for FGF21 delivery ( [email protected] ) for AKI treatment. [email protected] could be efficiently internalized by renal cells and exhibited antioxidative, antiapoptotic and anti-inflammatory effects. A septic AKI murine model was established to assess the in vivo performance of [email protected] The results showed that injected [email protected] specifically accumulated in the injured kidney and exerted good renoprotective effects. This study provides an innovative thread for precise drug delivery in the treatment of various renal diseases.
研究领域:
纳米技术
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药学
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生物医学工程
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肾脏生理学
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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
ACTA PHARMACOLOGICA SINICA
·
2016
·Vol. 37
·期 11
·1467-1480
·
IF 3.166
Fu Yu,Lin Qing,Gong Tao,Sun Xun,Zhang Zhi-rong
Aim: We previously reported a novel triptolide (TP)-glucosamine conjugate (TPG) that specifically accumulated in kidneys and protected renal function from acute ischemia/reperfusion (I/R) injury in rats. In this study we further examined the molecular mechanisms underlying the renoprotective action of TPG. Methods: The renal-targeting of TPG was investigated in a human proximal renal tubular epithelial cell line (HK-2) by measuring cell uptake of TP or TPG. The effects of TP or TPG on cell cycle distribution and apoptosis rate of HK-2 cells were assessed, and the activities of caspase-3 and caspase-9 were also measured. SD rats were subjected to bilateral renal ischemia by temporarily clamping both renal pedicles. The rats were administered TP (4.17 μmol·kg −1 ·d −1 , iv) or TPG (4.17 μmol·kg −1 ·d −1 , iv) for 3 d before the renal surgery. The kidneys were harvested after 24 h of recovery from the surgery. The levels of oxidative stress, proinflammatory cytokines, chemotactic cytokines and intracellular adhesion molecules in kidneys were examined. Results: The uptake of TPG in HK-2 cells was 2–3 times higher than that of TP at the concentrations tested. Furthermore, TPG targeting the proximal tubules was mediated through interactions with megalin receptors. TP (40–160 nmol/L) concentration-dependently increased G 2 /M arrest, apoptosis and caspase-3/caspase-9 activity in HK-2 cells, whereas the same concentrations of TPG did not show those features when compared with the control group. In I/R-treated rats, TPG administration caused more robust down-regulation of proinflammatory cytokines (TNF-α, IL-6, IL-1, TGF-β) and chemotactic cytokines (MCP-1) in the kidneys compared with TP administration, suggesting the inhibition of the proliferation and accumulation of lymphocytes. And TPG administration also caused more prominent inhibition on the levels of oxidative stress and intracellular adhesion molecules in the kidneys, compared with TP administration. Conclusion: The renal-targeting TPG is more effective and less toxic than TP, in amelioration of I/R-induced rat renal injury, which may provide a new avenue for the treatment of acute kidney injury.
研究领域:
药理学
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肾病学
·
分子生物学
✓ 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）