Acta Pharmaceutica Sinica B
·
2018
·
IF 6.014
Qian Zhang,Chuncao Xu,Shiqi Lin,Huanbin Zhou,Gangtao Yao,Hu Liu,Lili Wang,Xin Pan,Guilan Quan,Chuanbin Wu
Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.
研究领域:
中药学
·
免疫学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Jiangxiu Niu,Ming Yuan,Hongying Li,Yao Liu,Liye Wang,Yanli Fan,Yansong Zhang,Xianghui Liu,Lingmei Li,Jingxiao Zhang,Chenyu Zhao
Challenges associated with topical analgesics and anti-inflammatory drugs include poor drug penetration and retention at the desired lesion site. Therefore, improving these challenges would help to reduce the toxic and side effects caused by drug absorption into the systemic circulation and improve the therapeutic efficacy of topical therapeutic drugs. Pentapeptide (KTTKS) is a signal peptide in skin tissue, it can be recognized and bound by signal recognition particles. In the current study, we successfully prepared novel indomethacin (IMC) loaded KTTKS-modified ethosomes (IMC-KTTKS-Es), and the physicochemical properties and topical efficacy were investigated. Results showed that the prepared IMC-KTTKS-Es displayed a particle size of about 244 nm, a negative charge, good deformability, and encapsulation efficiency (EE) exceeding 80% for IMC, with a sustained release pattern. In vitro percutaneous permeation studies revealed that the skin retention was increased after the drug was loaded in the IMC-KTTKS-Es. Confocal laser scanning microscopy also showed improved skin retention of IMC-KTTKS-Es. In addition, IMC-KTTKS-Es showed improved topical analgesic and anti-inflammatory activity with no potentially hazardous skin irritation. This study suggested that the IMC-KTTKS-Es might be an effective drug carrier for topical skin therapy with a good safety profile.
研究领域:
药剂学
·
皮肤生物学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2012
·
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
·
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
POLYMER SCIENCE SERIES B
·
2015
·Vol. 57
·期 5
·530-537
·
IF 0.577
Ban Yingying,Wang Youfa
A kind of novel bioinspired polymeric material based on poly( D,L -lactic acid) was prepared. Firstly, the maleic anhydride (MA) grafted to PDLLA (PDLLA- g -MA) was synthesized, then PDLLA- g -MA reacted with Gly-Arg-Gly-Asp-Tyr (GRGDY) pentapeptide, which can give the biocompatibility and bioactivity to polymer. Then nano-hydroxyapatite (HAP) was added to enhance the hydrophilicity and cell adhesion of composite obtained. According to spectroscopy (FTIR, 13 C NMR) and pyrolysis-gas chromatography-mass spectrometry, PDLLA- g -MA and PDLLA- g -MA- g -GRGDY were synthesized successfully. Static water contact angle test, thermogravimetry, methylthiazolyl tetrazolium assay and scanning electron microscopy were used to characterize the properties of materials. The results show that the new composite material had better hydrophilicity and cell affinity than pure PDLLA, so it can be used as a potential composite membrane for tissue engineering application.
研究领域:
生物材料
·
组织工程
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 15
·3044-3053
·
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
·
药物分析
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2014
·Vol. 50
·期 1
·427-438
·
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
·
材料科学
·
药物化学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
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
·
免疫学
✓ 已验证
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.
研究领域:
生物化学
·
材料科学
·
医学检测
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 111
·110019-110031
·
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
·
生物医学工程
·
分子识别技术
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Huimin Chen,Jing Cheng,Xixi Cai,Jinzhi Han,Xu Chen,Lijun You,Caihua Xiong,Shaoyun Wang
Biofilm infection will cause chronic inflammation and hinder the normal healing process of wound. Here, based on the self-assembly of three designed amphiphilic pentapeptides named EK, GG, and DR, pH-switchable antibacterial hydrogels with amphiphilic fiber network are used for the eradication of biofilms and the rescue of delayed healing in infected wounds. These pentapeptides-based hydrogels exhibit an acidic pH-switchable antimicrobial effect and are biocompatible at neutral pH. Additionally, supramolecular nanofiber networks with physical cross-linking with thermosensitive polymers (PNIPAm) and loaded antibacterial oregano oil are further developed. In vitro experiments indicate that the antimicrobial activity of hydrogels comes from the disassembly of acidic pH-dependent nanofiber network and activated release of pentapeptides and oregano oil, which achieves synergistic biofilm eradication. Remarkably, DR-based supramolecular hydrogel improves the healing efficiency of the full-thickness wound of skin in vivo, which is manifested by increased wound closure rate, reduced inflammatory response, faster angiogenesis, and collagen deposition in the wound, exhibiting great potential as wound dressing. The proposed synergistic strategy of inhibiting biofilm formation and activating healing may provide an efficient method for the treatment of clinically infected wounds.
研究领域:
材料科学
·
生物材料
·
药学
·
伤口愈合
·
感染控制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD BIOTECHNOLOGY
·
2023
·
IF 1.8
Junxin Zhao,Maomao Ma,Zheling Zeng,Dongman Wan,Xianghui Yan,Jiaheng Xia,Ping Yu,Deming Gong
This study aimed to investigate the effect of mutating the consensus pentapeptide on the enzymatic properties and structural characteristics of Bacillus licheniformis lipase. Site-directed mutagenesis was used to construct mutants and then expressed in Escherichia coli BL21. After purification and enzyme activity analysis, only A75C and A75G retained activity. Compared to the wild-type lipase and A75G, the A75C showed higher thermostability at 40°C and better alkali resistance in pH 9.0–10.0 after incubation for 1 h. The kinetic parameters, structural characteristics and surface hydrophobicity of the lipases were determined. The results indicated that the secondary structure was hardly changed, while mutants exhibited higher activity, thermostability and hydrophobicity. Finally, the reasons for the increased enzyme activity were conducted through molecular dynamics simulation. The strategy of mutating the first residue of the lipase consensus pentapeptide may provide new insights into the enzyme engineering for industrial applications.
研究领域:
生物化学
·
酶学
·
蛋白质工程
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
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
·
癌症免疫治疗
·
分子生物学
·
药学
✓ 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）