INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2012
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IF 3.35
Yinhe Tan,Zhiwen Yang,Xin Pan,Meiwan Chen,Min Feng,Lili Wang,Hu Liu,Ziyun Shan,Chuanbin Wu
The objective of this study was to investigate the stability and aerosolization of pressurized metered dose inhalers (pMDIs) containing thymopentin nanoparticles . Thymopentin nanoparticles, fabricated by a bottom-up process, were suspended in hydrofluoroalkane (HFA) 134a together with cineole and/or n -heptane to produce pMDI formulations. The stability study of the pMDIs obtained was carried out at ambient temperature for 6 months. The amount of thymopentin and the aerosolization properties of pMDIs were determined using high-performance liquid chromatography (HPLC) and a twin-stage impinger (TSI), respectively. Based on the results, thymopentin nanoparticles were readily suspended in HFA 134a with the aid of cineole and/or n -heptane to form physically stable pMDI formulations, and more than 98% of the labeled amount of thymopentin and over 50% of the fine particle fraction (FPF) of the pMDIs were achieved. During storage, it was found that for all pMDIs more than 97% of the labeled amount of thymopentin and FPF greater than 47% were achieved. Moreover, the size of thymopentin nanoparticles in propellant containing cineole and n -heptane showed little change. It is, therefore, concluded that the pMDIs comprising thymopentin nanoparticles developed in this study were stable and suitable for inhalation therapy for systemic action.
研究领域:
药剂学
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药物递送系统
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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
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 15
·3044-3053
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IF 4.726
Chunbao Du,Xiaoling Hu,Ping Guan,Longxia Guo,Liwei Qian,Renyuan Song,Ji Li,Chaoli Wang
Novel water-compatible ionic liquid-functionalized microspheres with molecularly imprinted shell layer were controllably synthesized via precipitation polymerization and surface imprinting technique. Here, a room-temperature ionic liquid was synthesized to prepare these surface-imprinted microspheres with excellent water solubility and multiple binding sites with template molecules. The peptide drug thymopentin (TP5) was chosen as a template molecule, which is known as an immunomodulating agent. The as-prepared microspheres were fully characterized. Results reveal that ionic liquid incorporation significantly improves the adsorption of TP5. Moreover, the adsorption property and recognition capability towards TP5 are closely related to the synergetic effect of electrostatic interaction and hydrogen bonding. Through employing the synergetic effect of directional and non-directional interactions, the surface-imprinted microspheres exhibit high adsorption capacity, good selective recognition, and rapid binding ability for TP5. The surface-imprinted microspheres demonstrate potential usage for TP5 enrichment from other biomolecules, and the proposed method was successfully applied for TP5 determination in thymopentin injection and urine.
研究领域:
生物化学
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药物分析
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材料科学
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
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2014
·Vol. 50
·期 1
·427-438
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IF 2.305
Du Chunbao,Hu Xiaoling,Guan Ping,Guo Longxia,Qian Liwei,Li Ji,Song Renyuan,Tang Yimei
A novel water-compatible surface-imprinted core–shell microsphere, which had multiple non–covalent interactions with template molecule, was successfully prepared by the surface grafting polymerization method in acetonitrile–water systems with thymopentin as template through ionic liquid-functionalized polyethyleneglycolmethacrylate-co-vinylimidazole microsphere as the matrix. The average diameter of matrix was 1 μm ± 20 nm and the thickness of imprinted layer was about 50 nm. The results of static adsorption experiments indicated that ionic liquid-functionalized molecularly imprinted microspheres showed the good adsorption capacity and specific recognition for template peptide. The binding-isotherm analysis showed that Langmuir isotherm models gave a good fit in the range of concentrations, suggesting that there was only one kind of binding site in imprinted layer. Measurements of the binding kinetics revealed that surface-imprinted composite microspheres reached peptide-adsorption equilibrium in 60 min and the maximum adsorption capacity for TP5 was 38.4 mg g −1 . The effects of pH, salt concentration, and temperature on the adsorption capacities were investigated. The microspheres were found to have a high specificity for TP5 with little affinity for BSA and Hb. Finally, the core–shell microspheres can be reused with only 15.6 % decrease in TP5 adsorption capacity after six times.
研究领域:
生物化学
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材料科学
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药物化学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2017
·
IF 4.159
Shiqi Lin,Bingzhen Cai,Guilan Quan,Tingting Peng,Gangtao Yao,Chune Zhu,Qiaoli Wu,Hao Ran,Xin Pan,Chuanbin Wu
Thymopentin (TP5) is commonly used in the treatment for autoimmune diseases, with a short plasma half-life (30 s) and a long treatment period (7 days to 6 months). It is usually administrated by syringe injection, resulting in compromised patient compliance. Dissolving microneedle array (DMNA) offers a superior approach for transdermal delivery of biological macromolecules, as it allows painless penetration through the stratum corneum and generates minimal biohazardous waste after dissolving in the skin. Despite recent advances in DMNA as a novel approach for transdermal drug delivery, problem of insufficient mechanical strength remains to be solved. In this study, TP5-loaded DMNA (TP5-DMNA) was uniquely developed using a modified two-step molding technology. The higher mechanical strength was furnished by employing bovine serum albumin (BSA) as a co-material to fabricate the needles. The obtained TP5-DMNA containing BSA displayed better skin penetration and higher drug loading efficiency than that without BSA. The in vivo pharmacodynamics study demonstrated that TP5-DMNA had comparative effect on immunomodulation to intravenous injection of TP5, in terms of ameliorating the CD4+/CD8+ ratio, SOD activity and MDA value to the basal level. Only mild irritation was observed at the site of administration. These results suggest that the novel TP5-DMNA utilizing BSA provides an alternative approach for convenient and safe transdermal delivery of TP5, which is a promising administration strategy for future clinical application.
研究领域:
药剂学
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免疫学
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DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 111
·110019-110031
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IF 3.289
Xumian Gao,Xiaoling Hu,Ping Guan,Chunbao Du,Shichao Ding,Xiaoyan Zhang,Bangpeng Li,Xiongqi Wei,Renyuan Song
An approach for synthesizing core–shell imprinting polymers using P(EGDMA-CMS) microspheres prepared via dispersion polymerization as a core and employing a surface imprinting technique and iniferter-induced radical polymerization is described. N,N-Diethyldithiocarbamyl groups were immobilized on the surface of the supporting microspheres to form the surface iniferter and further prepare the imprinting layer. Thymopentin (TP5) was selected as the template molecule, which was known to be an immunomodulating agent that had medical properties. Here, a bifunctional ionic liquid (IL), namely, 1-vinyl-3-carbamoylmethyl-imidazolium chloride ([VACMIM]Cl), was synthesized and employed as a novel functional monomer on the basis of the demands of peptide imprinting and the designability of ILs. Under irradiation by UV light, the surface iniferter decomposed and then polymerization was initiated to form a thin surface imprinting layer with specific recognition cavities for TP5. The surface imprinting layer possessed a uniform thickness of ∼35 nm, which was beneficial for the mass transfer of the template TP5, owing to good control of the thickness of the imprinting layer by controlled/living radical polymerization (CRP). The polymeric microspheres were fully characterized and their adsorption properties were investigated. The surface molecular imprinting microspheres (SMIMs) displayed high binding affinity, good selective specificity, rapid adsorption equilibrium and satisfactory reusability. The Scatchard plots of the SMIMs could be fitted to one straight line, which suggested that there was only one kind of binding site. Furthermore, the method of combining a surface imprinting technique and CRP together can be extended to a wide range of applications for chemical sensors, drug delivery and the separation of biomacromolecules.
研究领域:
材料科学
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生物医学工程
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分子识别技术
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DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Zhang Xiaodian,Tian Hailong,Chen Yang,Liang Baichuan,Nice Edouard C.,Huang Canhua,Xie Na,Zheng Shaojiang
Immunotherapy has shown marked progress in promoting systemic anti-colorectal cancer (CRC) clinical effects. For further effectively sensitizing CRC to immunotherapy, we have engineered a pH-sensitive zeolitic imidazolate framework-8 (CS/NPs), capable of efficient cGAS-STING pathway activation and immune checkpoint blockade, by encapsulating the chemotherapeutic mitoxantrone (MTX) and immunomodulator thymus pentapeptide (TP5) and tailoring with tumor-targeting chondroitin sulfate (CS). In this nanoframework, CS endows CS/NPs with specific tumor-targeting activity and reduced systemic toxicity. Of note, the coordinated Zn2+ disrupts glycolytic processes and downregulates the expression of glucose transporter type 1 (GLUT1), thus depriving the cancer cells of their energy. Zn2+ further initiates the adenosine 5’-monophosphate activated protein kinase (AMPK) pathway, which leads to PD-L1 protein degradation and sensitizes CRC cells to immunotherapy. Moreover, the damaged double-stranded DNA during MTX treatment activates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which works together with TP5 induced the proliferation and differentiation of T lymphocytes and dendritic cells to further enhance the anti-CRC immune response. Therefore, CS/NPs efficiently sensitize cells to chemotherapy and stimulate systemic antitumor immune responses both in vitro and in vivo, representing a promising strategy to increase the feasibility of CRC immunotherapy.Graphical Abstract
研究领域:
纳米技术
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癌症免疫治疗
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Chen Yang,Tian Hailong,Zhang Xiaodian,Nice Edouard C.,Huang Canhua,Zhang Haiyuan,Zheng Shaojiang
Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs. This nanoassembly effectively accumulated in tumor sites through the copper transport mechanism. Meanwhile, TCe6@Cu/TP5 could induce mitochondrial impairment by photodynamic therapy (PDT) mediated reactive oxygen species (ROS) accumulation and Cu 2+ triggered cuproptosis, resulting in evoking the AMP-activated protein kinase (AMPK) pathway to degrade PD-L1, and activating the cGAS-STING pathway to enhance anti-tumor immunity. Moreover, TP5 significantly promoted the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to further amplify the cancer immunity cycle. Collectively, our TCe6@Cu/TP5 NPs effectively facilitate drug accumulation and activate systemic antitumor immunity in vitro and in vivo, providing an innovative solution across the BBB that potentiates GBM immunotherapy. Graphical
研究领域:
癌症研究
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纳米技术
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免疫学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 11.5
Jing Zuo,Yichun Huang,Hailong Tian,Siyuan Qin,Yonghao Yan,Han Yan,Yining Jiang,Lei Li,Shiqi Wang,Yongfeng Jia,Yuan Zhao,Canhua Huang
Disrupting mitochondrial metabolism and reactivating antitumor immunity offers a compelling strategy to enhance therapeutic outcomes in glioblastoma (GBM). Here, we report a mitochondria-targeting nanoplatform that integrates GBM-selective delivery, metabolic disruption, and immune activation for synergistic GBM therapy. The nanoplatform co-encapsulates L820—a conjugate of lonidamine (LND) and IR820 with mitochondrial affinity—and the immunomodulator TP5 into a ZIF-8 framework, which is coated with H-ferritin (HFn) for TfR1-mediated blood–brain barrier (BBB) penetration and GBM targeting. After endocytosis and GBM-specific, acid-triggered degradation, L820 accumulates in mitochondria and causes profound mitochondrial dysfunction, including membrane potential collapse, ATP depletion, and AMPK activation. Concurrently, Zn 2+ released from ZIF-8 suppresses GLUT1 and HIF-1α, impairing glycolysis and reducing CD47 expression. These dual metabolic stresses induce mitochondrial DNA (mtDNA) release and activate the cGAS–STING pathway, promoting type I interferon production and immunogenic cell death. TP5 enhances T cell activation while suppressing Tregs, further remodeling the GBM immune microenvironment. This mitochondria-focused strategy achieves potent metabolic interference and immune reprogramming for effective GBM treatment.
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产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2015
·
IF 2.711
Longxia Guo,Xiaoling Hu,Ping Guan,Chunbao Du,Dan Wang,Dongmen Song,Xumian Gao,Renyuan Song
Novel superparamagnetic surface-imprinted microspheres (SIMs) with molecularly imprinted shell layer were controllably synthesized via fragment imprinting and surface imprinting technique. The SIMs-Arg and SIMs-Lys microspheres were prepared by using L-arginine (L-Arg) and L-lysine (L-Lys) as pseudo-template molecule for specific rebinding to thymopentin (TP5), respectively. The characterization results revealed that both SIMs-Arg and SIMs-Lys were successfully prepared and possessed a high magnetic sensitivity. The rebinding-isotherm analyses of SIMs-Arg and SIMs-Lys showed that the Langmuir isotherm model was well fitted to the equilibrium data, indicating that only one kind of rebinding site was present in SIMs-Arg and SIMs-Lys. Besides, the kinetic properties of SIMs-Arg and SIMs-Lys both were well described by the pseudo-second-order kinetics model, which indicated that a chemical process may be the rate-limiting step in the rebinding process. Moreover, the magnetic imprinted microspheres were found to have a higher specificity for TP5 than that for immunostimulating peptide human (IPH). What is more, SIMs-Arg and SIMs-Lys were successfully applied for TP5 determination in urine. According to the maximum adsorption capacity, the imprinting factor and real sample experiment, it was noted that SIMs-Arg had better specific adsorption property for TP5 than SIMs-Lys.
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DOI
高影响因子
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