INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
·
IF 5.3
Yuying Chen,Qingwei He,Huangjie Lu,Jie Yang,Jiongming Han,Ying Zhu,Ping Hu
This study addresses the challenging task of quantitatively investigating drug release from PLGA microspheres after in vivo administration. The objective is to employ Förster resonance energy transfer (FRET) to visualize drug-encapsulated microspheres in both in vitro and in vivo settings. The primary goal is to establish a quantitative correlation between FRET fluorescence changes and microsphere drug release. The study selects drugs with diverse structures and lipid solubility to explore release mechanisms, using PLGA as the matrix material. Clozapine and risperidone serve as model drugs. FRET molecules, Cy5 and Cy5.5, along with Cy7 derivatives, create FRET donor–acceptor pairs. In vitro results show that FRET fluorescence changes align closely with microsphere drug release, particularly for the Cy5.5-Cy7 pair. In vivo experiments involve subcutaneous administration of microspheres to rats, tracking FRET fluorescence changes while collecting blood samples. Pharmacokinetic studies on clozapine and risperidone reveal in vivo absorption fractions using the Loo-Riegelman method. Correlating FRET and in vivo absorption data establishes an in vitro – in vivo relationship (IVIVR). The study demonstrates that FRET-based fluorescence changes quantitatively link to microsphere drug release, offering an innovative method for visualizing and monitoring release in both in vitro and in vivo settings, potentially advancing clinical applications of such formulations.
研究领域:
药剂学
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生物医学工程
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2020
·
IF 10.317
Fenfen Li,Tuanwei Li,Debo Zhi,Pengping Xu,Wenshen Wang,Yi Hu,Yuanyuan Zhang,Shaozhen Wang,J. Matula Thomas,J. Beauchamp Norman,Weiping Ding,Lifeng Yan,Bensheng Qiu
Encouraging progress in multifunctional nanotheranostic agents that combine photothermal therapy (PTT) and different imaging modalities has been made. However, rational designed and biocompatible multifunctional agents that suitfable for in vivo application is highly desired but still challenging. In this work, we rationally designed novel ultrasmall multifunctional nanodots (FS-GdNDs) by combining the bovine serum albumin (BSA)-based gadolinium oxide nanodots (GdNDs) obtained through a biomineralization process with a small-molecule NIR-II fluorophore (FS). The as-prepared FS-GdNDs with an ultrasmall hydrodynamic diameter of 9.3 nm exhibited prominent NIR-II fluorescence properties, high longitudinal relaxivity (10.11 mM −1 s −1 ), and outstanding photothermal conversion efficiency (43.99%) and photothermal stability. In vivo studies showed that the FS-GdNDs with enhanced multifunctional characteristics diaplayed satisfactory dual-modal MR/NIR-II imaging performance with a quite low dose. The imaging-guided PTT achieved successful ablation of tumors and effectively extended the survival of mice. Cytotoxicity studies and histological assay demonstrated excellent biocompatibility of the nanodots. Importantly, this novel FS-GdNDs can undergo efficient body clearance through both hepatobiliary and renal excretion pathways. The novel ultrasmall multifunctional FS-GdNDs with excellent features hold tremendous potential in biomedical and clinical applications.
研究领域:
纳米技术
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生物医学工程
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诊疗学
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分子影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2018
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IF 3.115
Hongyan Ma,Qi Huang,Wenshan Qu,Linyuan Li,Min Wang,Shao Li,Fujiang Chu
Ethnopharmacological relevance The dried roots of Sophora flavescens Ait. (Leguminosae) is traditionally used as antipyretic medicine to reduce inflammation. It is well known that alkaloids and flavonoids are the main constituents of S. flavescens . However, the clinical researches and applications of S. flavescens is mainly based on its water-extracted alkaloids, its flavonoids may still remain in residues and have been underused. With development and manufacturing of S. flavescens in recent years, more herb residues are being produced. Since they are typically treated as waste and dumped openly in landfill sites, which can cause pollution, there is a great need to explore these wastes as recyclable resources and increase their added value. To date, whether other bioactive components would be found in the residues of S. flavescens is still unknown. If the extraction method of these active ingredients was established, the residues of S. flavescens could be turned from the harm to a benefit and make great sense of the comprehensive utilization of S. flavescens resources. This study aimed to establish an extraction method of the residues of S. flavescens and investigate the anti-inflammatory effect of it both in vivo and in vitro . Materials and methods Dried S. flavescens were decocted with distilled water firstly, then the residues were powdered and extracted with ethyl acetate by using ultrasonic wave. HPLC was utilized to analyze the chemical constituents of the water extracts of S. flavescens (WSF) and the ethyl acetate extracts of residues of S. flavescens (RSF). In vivo , the anti-inflammatory effect of WSF and RSF were evaluated using the xylene-induced auricle edema, acetic acid-induced peritoneal permeability and carrageenan-induced hind paw edema methods. In vitro, the inhibitory activities of WSF and RSF on NO, TNF-α, IL-6 and MCP-1 production of LPS-treated RAW264.7 cells were measured. Results The major ingredients of RSF were flavonoids, while WSF almost had no flavonoids. In vivo , WSF and RSF (200 mg/kg) could significantly inhibit the edema in the xylene-induced mice auricle edema and carrageenan-induced hind paw edema as well as the peritoneal permeability increased by acetic acid. They can also lower production levels of PGE 2 in inflamed paw tissues. In vitro experimental results showed that RSF (25-100 μg/mL) could significantly inhibit the release of pro-inflammatory cytokines NO, TNF-α, IL-6 and MCP-1 on LPS-induced RAW264.7 cells. The in vitro suppress effect of WSF had no dose-response relationship. Conclusions The residues of S. flavescens had obvious flavonoids with anti-inflammatory activity. This study provided evidence for the reuse of residues from S. flavescens in the food additive , medicine and cosmetic industries.
研究领域:
药理学
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民族药理学
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化学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2016
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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
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 15
·4481
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IF 4.412
Meng Cheng,Qiaoming Liu,Tiantian Gan,Yuanying Fang,Pengfei Yue,Yongbing Sun,Yi Jin,Jianfang Feng,Liangxing Tu
Prolonging in vivo circulation has proved to be an efficient route for enhancing the therapeutic effect of rapidly metabolized drugs. In this study, we aimed to construct a nanocrystal-loaded micelles delivery system to enhance the blood circulation of docetaxel (DOC). We employed high-pressure homogenization to prepare docetaxel nanocrystals (DOC(Nc)), and then produced docetaxel nanocrystal-loaded micelles (DOC(Nc)@mPEG-PLA) by a thin-film hydration method. The particle sizes of optimized DOC(Nc), docetaxel micelles (DOC@mPEG-PLA), and DOC(Nc)@mPEG-PLA were 168.4, 36.3, and 72.5 nm, respectively. The crystallinity of docetaxel was decreased after transforming it into nanocrystals, and the crystalline state of docetaxel in micelles was amorphous. The constructed DOC(Nc)@mPEG-PLA showed good stability as its particle size showed no significant change in 7 days. Despite their rapid dissolution, docetaxel nanocrystals exhibited higher bioavailability. The micelles prolonged the retention time of docetaxel in the circulation system of rats, and DOC(Nc)@mPEG-PLA exhibited the highest retention time and bioavailability. These results reveal that constructing nanocrystal-loaded micelles may be a promising way to enhance the in vivo circulation and bioavailability of rapidly metabolized drugs such as docetaxel.Keywords:nanocrystals;micelles;circulation;in vivo;docetaxel
研究领域:
药剂学
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生物医学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2023
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IF 4.9
Fulong Man,Yinqian Yang,Haisheng He,Jianping Qi,Wei Wu,Yi Lu
In vitro dissolution that predicts the in vivo performance of solid preparations is extremely important in formulation optimization. Fraction absorbed (Fa) has been used to screen in vitro dissolution protocols based on the idea of in vitro–in vivo correlation (IVIVC) but failed to increase the success rate due to the inaccuracy of the Fa. The essence of IVIVC is the correlation between in vitro dissolution and in vivo dissolution. We tried to establish in vitro dissolution protocol via similarity with in vivo dissolution using aripiprazole (APZ) as a model drug. Hybrid APZ crystals (APZ-HCs) were prepared by physically embedding aggregation-caused quenching (ACQ) fluorophores inside the lattice to measure the in vivo dissolution. The process did not change the physicochemical properties and crystallinity of APZ. The fluorophore illuminated APZ crystals but was quenched upon dissolution of APZ-HCs in aqueous media, enabling monitoring intact APZ-HCs in real-time. The good correlation between fluorescent quenching and dissolution of APZ-HCs justified reliable quantification of intact APZ crystals. The residual percentage of fluorescence intensity in rats treated by APZ-HCs was recorded with time, which was converted to in vivo dissolution by the difference from 100%. The in vivo dissolution was validated with the Fa. The in vitro dissolution profile of APZ was set up via a similarity factor larger than 50 in comparison with the in vivo dissolution. The study provides a novel idea and method to establish in vitro dissolution protocol.
研究领域:
药剂学
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药物递送系统
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Danilo de Souza Costa,Rayssa A. Cajas,Carla Monteiro Leal,Lara S. Aleixo de Carvalho,Lara Cruz de Souza,Lucas Fukui-Silva,Josué de Moraes,Ademar A. Da Silva Filho
Ethnopharmacological relevance Acmella oleracea (L.) R. K. Jansen, commonly referred to as “Jambu”, is a valuable medicinal plant native to the Amazon regions. Inflorescences of A. oleracea is utilized as local anesthetic properties and for its insecticidal, antiparasitic, and anthelmintic attributes. Aims of this study This study aimed to evaluate the in vitro and in vivo antiparasitic properties of A. oleracea extract and spilanthol (SPL) against Schistosoma mansoni . Materials and methods The ethanolic extract of A. oleracea inflorescences (AoE) was prepared, analyzed by HPLC-DAD, and characterized by UHPLC-HRMS/MS. SPL was isolated from AoE by chromatographic fractionation. The antischistosomal properties of AoE and SPL were evaluated in vitro against adult schistosomes and in preclinical assays using murine models of patent S. mansoni infection. Results Through UHPLC-HRMS/MS analysis, 14 alkamides were annotated in AoE. HPLC-DAD analysis of AoE revealed a peak with a substantial relative area of ∼85%, which was isolated and identified as SPL. AoE and SPL caused mortality of adult schistosomes ex vivo , showing EC 50 values of 32.6 μg/mL and 27.8 μM, respectively, without affected Vero cells or Caenorhabditis elegans . In preclinical studies, the oral administration (400 mg/kg) of AoE and SPL resulted in significant reductions in worm burden of 28% and ∼42%, respectively. Additionally, SPL exhibits remarkable effects on oogram, decreasing egg burden and the number of immature eggs by over 80%, while also promoting significant reductions in hepato- and splenomegaly. Conclusions The research underscores the antischistosomal activity of A. oleracea highlighting the potential of SPL as a lead for the development of new schistosomicidal drugs and encouraging further studies to validate the traditional anthelmintic use of A. oleracea inflorescences.
研究领域:
药理学
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寄生虫学
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药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 6
·744
·
IF 4.9
Qianqian Long,Xinmin Zhao,Lili Gao,Mengyuan Liu,Feng Pan,Xihui Gao,Changyou Zhan,Yang Chen,Jialei Wang,Jun Qian
Background:Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored.Methods:The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method. The cellular uptake efficiency of IR783-sLip was characterized by flow cytometry and fluorescence microscope imaging. The effects of IR783 density on liposomal in vivo behavior were investigated by pharmacokinetic studies, biodistribution studies, and in vivo imaging. The constitution of protein corona was analyzed by the Western blot assay.Results:Dense IR783 modification improved cellular uptake of liposomes in vitro but hindered their blood retention and tumor imaging performance in vivo. We found a correlation between IR783 density and protein corona absorption, particularly IgM, which significantly impacted the liposome performance. Meanwhile, we observed that increasing IR783 density did not consistently improve the effectiveness of tumor imaging.Conclusions:Increasing the density of modified IR783 on liposomes is not always beneficial for tumor near-infrared (NIR) imaging yield. It is not advisable to prematurely evaluate novel nanomaterials through fluorescence dye conjugation without carefully optimizing the density of the modifications.
研究领域:
药剂学
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生物医学工程
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分子影像学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
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2025
·Vol. 192
·期 4
·1-12
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IF 5.3
Zhou Xiayu,Wang Yue,Song Jiayi,Xiong Lihao,Zhao Xin,Chen Sihan,Zhao Weichao,Li Le,Zhen Deshuai
Three types of carbon dots were synthesized using the same precursor (folic acid and europium nitrate) via different preparation methods (doping and direct coordination). A comprehensive comparison and analysis of the morphology, surface groups, and optical properties of the prepared carbon dots (CD), europium-doped carbon dots (CD-Eu), and europium-functionalized carbon dots (CD@Eu) were conducted. Moreover, due to the higher quantum yield, excellent stability, and outstanding selectivity for UO 2 2+ exhibited by CD-Eu, we selected CD-Eu as the probe for subsequent applications. CD-Eu showed a sensitive response to UO 2 2+ within the concentration range 25 ~ 200 nM, with a detection limit of 0.84 nM (0.42 μg·L −1 ). Additionally, CD-Eu demonstrated excellent accuracy and recovery in spiked detection of real water samples. Furthermore, we discovered that this probe could detect UO 2 2+ both in vitro and in viv o. This strategy provides a promising fluorescent sensor for the detection of UO 2 2+ in water and biological samples, holding significant implications for addressing UO 2 2+ contamination issues. Graphical abstract
研究领域:
材料科学
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环境科学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
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IF 3.902
Bin’en Nie,Haiyong Ao,Teng Long,Jianliang Zhou,Tingting Tang,Bing Yue
Bacitracin immobilized on the titanium (Ti) surface significantly improves anti-bacterial activity and biocompatibility in vitro . In the current study, we investigated the biologic performance (bactericidal effect and bone-implant integration) of bacitracin-modified Ti in vivo . A rat osteomyelitis model with femoral medullary cavity placement of Ti rods was employed to analyze the prophylactic effect of bacitracin-modified Ti (Ti-BC). Thirty-six female Sprague Dawley (SD) rats were used to establish the Ti implant-associated infection. The Ti and Ti-BC rods were incubated with and without Staphylococcus aureus to mimic the contaminated Ti rod and were implanted into the medullary cavity of the left femur, and sterile Ti rods were used as the blank control. After 3 weeks, the bone pathology was evaluated using X-ray and micro-computed tomography (micro-CT) analysis. For the investigation of the Ti-BC implant osseointegration in vivo , fifteen SD rats were divided into three groups (N = 5), namely Ti, Ti-dopamine immobilized (Ti-DOPA), and Ti-BC. Ti rods were implanted into the left femoral cavity and micro-CT and histological evaluation was conducted after 12 weeks. The in vivo study indicated that Ti-immobilized bacitracin owned the prophylaxis potential for the infection associated with the Ti implants and allowed for the osseointegration. Thus, the multiple biofunctionalized Ti implants could be realized via immobilization of bacitracin, making them promising candidates for preventing the Ti implant-associated infections while retaining the osseointegration effects.
研究领域:
生物材料学
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医学工程
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
VETERINARY PARASITOLOGY
·
2023
·
IF 2.6
Shun Zhou,Liwei Xia,Jing Dong,Yongtao Liu,Qiuhong Yang,Ning Xu,Yibin Yang,Xiaohui Ai
Monogenean parasites pose a significant challenge to aquaculture, leading to adverse effects on fish health and yields. Current anthelmintic treatments for monogeneans have demonstrated limited efficacy and are further complicated by potential issues, which emphasize the necessity for effective and safe therapeutic strategies to manage monogeneans in aquaculture. In this study, in vivo and in vitro anthelmintic activity of febantel against Gyrodactylus kobayashii on goldfish ( Carassius auratus ), as well as its toxicity to goldfish were evaluated. In vivo assays indicated that febantel exhibited potent anthelmintic activity against G. kobayashii with an EC 50 value of 0.03 mg/L and 100 % anthelmintic efficacy at 0.1 mg/L after 48 h of exposure. Moreover, in vivo trials also revealed a notable post-treatment effect of febantel, where infected goldfish transferred to drug-free water after short 6-h exposure could still result in full eradication of the worms, indicating febantel might induce persistent perturbations in parasite physiology. In vitro assays showed a negative correlation between febantel concentrations and the survival of G. kobayashii . However, increasing the febantel concentration to 2.0 mg/L did not result in the complete death of all worms. Oral administration of febantel demonstrated limited anthelmintic activity, with only 49 % efficacy at a dosage of 200 mg/kg body weight daily over five days. Acute toxicity assays revealed the 48-h LC 50 value of febantel was 5.47 mg/L, which was 182.23 times higher than the 48-h EC 50 value, indicating that febantel has a favorable safety profile. However, febantel exposure potentially interfered with hepatic metabolism and oxidative status, as indicated by variations in SOD , GST , and P450 gene expression. In conclusion, treatment with 0.1 mg/L febantel for 24 h completely eradicated G. kobayashii infection on goldfish, demonstrating febantel’s potent anthelmintic activity. Coupled with its safety profile and extended post-treatment effectiveness, febantel is a promising candidate for controlling Gyrodactylus infections in aquaculture.
研究领域:
水产养殖学
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寄生虫学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Huan Tang,Sheng-Tao Yang,Yi-Fan Yang,Da-Ming Ke,Jia-Hui Liu,Xing Chen,Haifang Wang,Yuanfang Liu
As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 μmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.
研究领域:
生物医学
·
药理学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）