Journal of Materials Chemistry B
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2019
·Vol. 8
·期 5
·928-934
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IF 5.047
Jinzhu Mao,Hua Wang,Ying Xie,Yangxue Fu,Yuce Li,Pei Liu,Hongyao Du,Jinjin Zhu,Liyun Dong,Mubashir Hussain,Yan Li,Lianbin Zhang,Jintao Zhu,Juan Tao
Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 μm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion ex vivo. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.
研究领域:
药理学
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生物医学工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Microorganisms
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2022
·Vol. 10
·期 3
·503
·
IF 4.926
Huanli An,Tian Gan,Ming Tang,Hui Chen
Leptographium qinlingensisis a fungal symbiont of the Chinese white pine beetle (Dendroctonus armandi) and a pathogen of the Chinese white pine (Pinus armandii) that must overcome the terpenoid oleoresin defenses of host trees to invade and colonize.L. qinlingensisresponds to monoterpene flow with abundant mechanisms that include the decomposing and use of these compounds as a nitrogen source. Target of Rapamycin (TOR) is an evolutionarily conserved protein kinase that plays a central role in both plants and animals through integration of nutrients, energies, hormones, growth factors and environmental inputs to control proliferation, growth and metabolism in diverse multicellular organisms. In this study, in order to explore the relationship betweenTORgene and carbon sources, nitrogen sources, host nutrients and host volatiles (monoterpenoids) inL. qinlingensis, we set up eight carbon source treatments, ten nitrogen source treatments, two host nutrients and six monoterpenoids (5%, 10% and 20%) treatments, and prepared different media conditions. By measuring the biomass and growth rate of mycelium, the results revealed that, on the whole, the response ofL. qinlingensisto nitrogen sources was better than carbon sources, and the fungus grew well in maltose (carbon source), (NH4)2C2O4(inorganic nitrogen source), asparagine (organic nitrogen source) andP. armandii(host nutrient) versus other treatments. Then, by analyzing the relationship betweenTORexpression and different nutrients, the data showed that: (i)TORexpression exhibited negative regulation in response to carbon sources and host nutrition. (ii) The treatments of nitrogen sources and terpenoids had positively regulatory effects onTORgene; moreover, the fungus was most sensitive to β-pinene and 3-carene. In conclusion, our findings reveal thatTORinL. qinlingensisplays a key role in the utilization of host volatiles as nutrient intake, overcoming the physical and chemical host resistances and successful colonization.Keywords:Leptographium qinlingensis;Target of Rapamycingene;carbon sources;nitrogen sources;host nutrition;terpenoids
研究领域:
真菌学
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植物病理学
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分子生物学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 7
·1404
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IF 6.525
Yali Lin,Ruomei Shao,Tong Xiao,Shuqing Sun
Interest in transdermal delivery methods for stimulating hair regrowth has been increasing recently. The microneedle approach can break the barrier of the stratum corneum through puncture ability and improve drug delivery efficiency. Herein, we report a dissolvable microneedle device for the co-delivery of rapamycin and epigallocatechin gallate nanoparticles that can significantly promote hair regeneration. Compared with the mice without any treatment, our strategy can facilitate hair growth within 7 days. Higher hair shaft growth rate and hair follicle density with inconspicuous inflammation were exhibited in C57BL/6 mice, elucidating its potential for clinical application.Keywords:hair regrowth;microneedles;nanoparticles;rapamycin
研究领域:
药理学
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皮肤科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Dickson Pius Wande,Yue Qiu,Shijie Chen,Lan Yao,Yanghui Xu,Jing Yao,Hui Xiong
Oxaliplatin (OXA) and rapamycin (RAPA) combination therapy have shown the advantages of synergistically inhibiting the growth of cancer cells by enhancing apoptosis in cancerous cell lines. However, drug resistance and the lack of an orally administered formulation which exhibited the best clinical dosing compliance limited the clinical application of this regimen. Here, we report a nanogel-polymersomes drug delivery system (i.e.TMOR-CDAN) based on modified chitosan, chitosan diacetate (CDA), methoxy-poly-(ethylene glycol)-b-poly (lactide) (MPP), and D-alpha-tocopheryl polyethylene glycol succinate (TPGS) with permeation-glycoprotein (P-gp) inhibition capability for enhancing the oral chemotherapy efficacy of erroneously soluble RAPA and its synergistic chemotherapy with OXA. Hydrophilic OXA and hydrophobic RAPA were co-loaded using MPP and TPGS-based polymer capsules (i.e. TMOR), which were further coated by chitosan-modified gel to form TMOR-CDAN. The TMOR-CDAN displayed higher stability in both acidic and basic pH than free OXA and RAPA and could withstand the harsh gastric environmental conditions, preventing the burst drugs release while releasing the co-loaded drugs in a sustained and controlled manner. The dual-drug-loaded TMOR-CDAN provides a bifunctional platform for synergistic tumor therapy. Compared with the single drug OXA, RAPA, or the OXA and RAPA mixtures (OR), the TMOR-CDAN showed more outstanding in vitro cytotoxicity and in vivo antitumor chemotherapeutic efficacy, endowing the TMOR-CDAN with a prodigious potential for futuristic cancer chemotherapy .
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
高影响因子
Pharmaceutics
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2023
·Vol. 15
·期 3
·849
·
IF 5.4
Yanlong Yin,Hong Jiang,Yue Wang,Longyao Zhang,Chunyan Sun,Pan Xie,Kun Zheng,Shaoqing Wang,Qian Yang
Nanodelivery systems combining photothermal therapy (PTT) and chemotherapy (CT), have been widely used to improve the efficacy and biosafety of chemotherapeutic agents in cancer. In this work, we constructed a self-assembled nanodelivery system, formed by the assembling of photosensitizer (IR820), rapamycin (RAPA), and curcumin (CUR) into IR820-RAPA/CUR NPs, to realize photothermal therapy and chemotherapy for breast cancer. The IR820-RAPA/CUR NPs displayed a regular sphere, with a narrow particle size distribution, a high drug loading capacity, and good stability and pH response. Compared with free RAPA or free CUR, the nanoparticles showed a superior inhibitory effect on 4T1 cells in vitro. The IR820-RAPA/CUR NP treatment displayed an enhanced inhibitory effect on tumor growth in 4T1 tumor-bearing mice, compared to free drugs in vivo. In addition, PTT could provide mild hyperthermia (46.0 °C) for 4T1 tumor-bearing mice, and basically achieve tumor ablation, which is beneficial to improving the efficacy of chemotherapeutic drugs and avoiding damage to the surrounding normal tissue. The self-assembled nanodelivery system provides a promising strategy for coordinating photothermal therapy and chemotherapy to treat breast cancer.Keywords:nanodelivery system;rapamycin;curcumin;chemo-phototherapy;breast cancer
研究领域:
肿瘤学
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药剂学
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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
Advanced Science
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2023
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IF 15.1
Huiyun Li,Yusong Yuan,Lingpu Zhang,Chun Xu,Hailin Xu,Zhiwei Chen
Osteoarthritis (OA) is a chronic joint disease characterized by synovitis and joint cartilage destruction. The severity of OA is highly associated with the imbalance between M1 and M2 synovial macrophages. In this study, a novel strategy is designed to modulate macrophage polarization by reducing intracellular reactive oxygen species (ROS) levels and regulating mitochondrial function. A ROS-responsive polymer is synthesized to self-assemble with astaxanthin and autophagy activator rapamycin to form nanoparticles (NP@Poly RHAPM ). In vitro experiments show that NP@Poly RHAPM significantly reduced intracellular ROS levels. Furthermore, NP@Poly RHAPM restored mitochondrial membrane potential, increased glutathione (GSH) levels, and promoted intracellular autophagy, hence successfully repolarizing M1 macrophages into the M2 phenotype. This repolarization enhanced chondrocyte proliferation and vitality while inhibiting apoptosis. In vivo experiments utilizing an anterior cruciate ligament transection (ACLT)-induced OA mouse model revealed the anti-inflammatory and cartilage-protective effects of NP@Poly RHAPM , effectively mitigating OA progression. Consequently, the findings suggest that intra-articular delivery of ROS-responsive nanocarrier systems holds significant promise as a potential and effective therapeutic strategy for OA treatment.
研究领域:
药理学
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生物医学工程
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骨科
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免疫学
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Jiaoxiang Chen,Xin Gan,Shenkai Su,Sizhe Jiao,Zailing Gong,Ziqiang Liu,Xiaopei Wu,Jun Jiang,Jiaming Zhang,Junlai Wan
Intervertebral disc degeneration (IVDD) is a multifaceted and complex condition primarily driven by excessive inflammation, degradation of the extracellular matrix (ECM), and dysfunction of nucleus pulposus cells (NPCs). Despite extensive exploration of various therapeutic agents targeting IVDD, their efficacy remains disappointingly limited. This study underscores the efficacy of ginkgetin (GK), a natural bioflavonoid with potent anti-inflammatory properties, in mitigating inflammation as well as ECM degradation and NPC dysfunction triggered by interleukin-1β (IL-1β). However, GK alone cannot fully address the persistent obstruction in autophagic flux induced by IL-1β. To overcome this limitation, an innovative MMP13-responsive nanoplatform was developed, orchestrating the sequential delivery of GK and rapamycin (RA), targeting distinct phases of IVDD progression. In this design, GK is progressively released from exosomes during the initial phase, while RA is released from mesoporous silica nanoparticles during the mid-phase to enhance autophagic flux. This staged release approach leverages the strengths of both agents, addressing inflammation and restoring autophagy more effectively. In vivo experiments confirmed the substantial therapeutic benefits of this staggered delivery strategy in IVDD. The engineered MMP13-responsive nanoplatform represents a significant advancement in controlled, sequential drug delivery systems, offering a promising therapeutic avenue to effectively regulate inflammation and autophagy, thereby ameliorating IVDD.
研究领域:
医学
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生物材料学
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药理学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
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IF 8.7
Guangyong Lin,Huirong Huang,Meng Sun,Zhinan He,Shengjie Li,Xindan Liang,Yuqi Yan,Chenyu Qiu,Shize Li,Xinyu Zhao,Wanling Zhu,Longfa Kou,Ruijie Chen
Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a "two-stage" drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. In vitro and in vivo experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment.
研究领域:
药学
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生物医学工程
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骨科
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纳米技术
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药物递送
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产品关联
DOI
PubMed
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
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2024
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IF 1.6
Yuanxia Yang,Miaoting Yang,Lijuan Wang,Liufang He,Tao Shi
Background: The establishment and validation of methods for testing biological samples are crucial steps in pharmacokinetic studies. Currently, several methodological reports have been published on the detection of rapamycin plasma concentrations. Objective: The objective of this study was to explore an effective method for detecting rapamycin in rat whole blood biological samples. Method: In this study, we designed a rapid, sensitive, and specific liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) methodology for detecting rapamycin in rat whole blood biological samples. We comprehensively validated the specificity, linear range, lower limit of quantification (LLOQ), precision, accuracy, recovery, and stability of this method. Results: The findings of this study confirmed the successful implementation of LC-MS/MS for the detection of rapamycin, demonstrating its sensitivity, specificity, and reliability in quantitative analysis. This method ensures the accuracy and reliability of subsequent study data through our validated LC-MS/MS approach. Conclusion: The results demonstrated the successful implementation of an LC-MS/MS method for sensitive, specific, and reliable quantitative analysis of rapamycin in rat whole blood samples. This method ensures the accuracy and reliability of subsequent study data. Significance: The importance of this study lies in the successful establishment of a rapid, sensitive, and specific LC-MS/MS method for detecting rapamycin concentration in rat whole blood, ensuring the accuracy and reliability of subsequent research data. This provides a crucial tool and foundation for further understanding the metabolism and pharmacological effects of rapamycin in vivo, aiding in the advancement of drug research and clinical applications in related fields.
研究领域:
药代动力学
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药物分析
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生物样本检测
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Huirong Huang,Xindan Liang,Shengjie Li,Yuqi Yan,Shize Li,Chenyu Qiu,Zhanzheng Ye,Yixuan Zhu,Dingchao Shen,Yinhao Lin,Luhui Wang,Nuo Chen,Yinsha Yao,Xinyu Zhao,Fugen Wu,Xianbao Shi,Longfa Kou,Ruijie Chen,Qing Yao
Osteoarthritis (OA) is a prevalent chronic disease, characterized by the destruction of joint cartilage and synovitis, affects over 7 % of people worldwide. Disease-modifying treatments for OA still face significant challenges. Chondrocytes, as the exclusive cellular component of articular cartilage, play a pivotal role in synthesizing the intricate matrix of cartilage, thereby assuming a critical responsibility in facilitating its renewal and repair processes. However, oxidative stress within chondrocytes and subsequent apoptotic cell death plays significant roles in the progression of OA. Therefore, targeting apoptosis inhibition and mitigation of oxidative stress in chondrocytes represents a promising therapeutic strategy for OA. This study develops a type II collagen-targeting peptide (WYRGRLC) modified bilirubin/rapamycin carrier-free nanoparticle (PP/BRRP) and evaluate its therapeutic potential for OA. The PP/BRRP system exhibits remarkable chondrocyte-targeting ability, enabling the rupture of highly oxidized chondrocytes and subsequent release of bilirubin and rapamycin. This dual payload effectively scavenges reactive oxygen species, triggers autophagy, and suppresses the mTOR pathway, thereby augmenting anti-inflammatory and anti-apoptotic effects. The in vivo experiments further validate the retention and therapeutic efficacy of PP/BRRP in rat joints affected by OA. Overall, PP/BRRP exhibits significant potential for intervention and treatment of OA.
研究领域:
药理学
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纳米技术
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风湿病学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Qi Wang,Jiaxin Dong,Mengxian Du,Xinna Liu,Shiqi Zhang,Di Zhang,Wanyun Qin,Xikun Xu,Xianghui Li,Ruidong Su,Leyi Qiu,Baoqiang Li,Huiping Yuan
Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications.Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined.Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function.Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.
研究领域:
眼科
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药学
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神经科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
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2023
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IF 5.4
Jihua Tian,Jing Wang,Huanyu Xu,Bocheng Zou,Weihao Chen,Yulong Liu,Jingshu Chen,Ruiping Zhang
Rapamycin has great potential in the antitumor application, but its therapeutic effect is seriously affected by poor water solubility, targeting ability, and low bioavailability. Here, we constructed a novel composite nanomaterial with PCN-224 as a drug carrier and loaded rapamycin, named [email protected] @HA. The nanoplate not only improves targeting, but also synergizes rapamycin with PCN-224 to effectively promote tumor cell apoptosis , which subsequently causes immunogenic cell death (ICD), and shows strong therapeutic effect in 4T1 breast cancer model. The treatment effect depends on three main points:(i)Proapoptotic effect of rapamycin on tumor cells;(ii)ROS production by PCN-224-mediated photodynamic therapy;(iii)ICD induced DC maturation, increased immune response and promoted T cell proliferation and differentiation. This nanoplate offers potential antitumor efficacy in combination with chemotherapy, photodynamic therapy, and immunotherapy .
研究领域:
癌症研究
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纳米技术
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免疫疗法
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药学
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生物医学工程
✓ 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）