INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qingyu Lu,Wenhao Gao,Zhenzhen Chen,Zhihong Liu,Jie Wang,Lingjun Zeng,Xiaomu Hu,Enqin Zheng,Qian Zhang,Hongtao Song
Ovarian cancer is a malignant tumor that seriously endangers the lives of women, with chemotherapy being the primary clinical treatment. However, chemotherapy encounters the problem of generating multidrug resistance (MDR), mainly due to drug efflux induced by P-glycoprotein (P-gp), which decreases intracellular accumulation of chemotherapeutic drugs. The drugs efflux mediated by P-gp requires adenosine triphosphate (ATP) hydrolysis to provide energy. Therefore, modulating energy metabolism pathways and inhibiting ATP production may be a potential strategy to reverse MDR. Herein, we developed a PTX-ATO-QUE nanoparticle (PAQNPs) based on a PLGA-PEG nanoplatform capable of loading the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor atovaquone (ATO), the glycolysis inhibitor quercetin (QUE), and the chemotherapeutic drug paclitaxel (PTX) to reverse MDR by inhibiting energy metabolism through multiple pathways. Mechanistically, PAQNPs could effectively inhibit the OXPHOS and glycolytic pathways of A2780/Taxol cells by suppressing the activities of mitochondrial complex III and hexokinase II (HK II), respectively, ultimately decreasing intracellular ATP levels in tumor cells. Energy depletion can effectively inhibit cell proliferation and reduce P-gp activity, increasing the chemotherapeutic drug PTX accumulation in the cells. Moreover, intracellular reactive oxygen species (ROS) is increased with PTX accumulation and leads to chemotherapy-resistant cell apoptosis. Furthermore, PAQNPs significantly inhibited tumor growth in the A2780/Taxol tumor-bearing NCG mice model. Immunohistochemical (IHC) analysis of tumor tissues revealed that P-gp expression was suppressed, demonstrating that PAQNPs are effective in reversing MDR in tumors by inducing energy depletion. In addition, the safety study results, including blood biochemical indices, major organ weights, and H&E staining images, showed that PAQNPs have a favorable in vivo safety profile. In summary, the results suggest that the combined inhibition of the two energy pathways, OXPHOS and glycolysis, can enhance chemotherapy efficacy and reverse MDR in ovarian cancer.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Zhiting Sun,Xiaoxiao Wang,Jing Liu,Zhihong Wang,Weiwei Wang,Deling Kong,Xigang Leng
Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. Specifically, the NO donor l-arginine (l-Arg) and the photosensitizer indocyanine green (ICG) were co-encapsulated in poly(lactic-glycolic acid) (PLGA) nanoparticles and then loaded into the poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL–PEG–PCL) hydrogel to develop an injectable, thermosensitive dual drug delivery system (PLGA@ICG@l-Arg/Gel). Significantly, reactive oxygen species (ROS) produced by PLGA@ICG@l-Arg/Gel under near-infrared (NIR) light irradiation could not only result in the apoptosis of cancer cells but also oxidize l-Arg to generate NO, which could suppress the proliferation of cancer cells. Moreover, ROS could further oxidize NO to generate peroxynitrite anions (ONOO–). ONOO– could activate matrix metalloproteinases (MMPs), which notably degraded collagen in ECM so as to damage the tumor microenvironment. PLGA@ICG@l-Arg/Gel significantly increased the antitumor efficacy against highly malignant 4T1 tumors in mice. Taken together, PLGA@ICG@l-Arg/Gel is a multifunctional platform that provides a novel strategy for cancer treatment with cascade amplification of the ROS oxidation effect, which holds great potential in clinical translation.
研究领域:
癌症治疗
·
药物递送系统
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 8
·期 23
·1900965
·
IF 6.27
Yao Yang,Zhengwei Huang,Jinyuan Li,Ziran Mo,Ying Huang,Cheng Ma,Wenhao Wang,Xin Pan,Chuanbin Wu
Combination therapy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR TKIs) with other chemotherapeutic agents is a feasible strategy to overcome resistance that often occurs after 9–13 months of EGFR TKIs administration in nonsmall cell lung cancer (NSCLC). In this study, a pulmonary microspheres system that codelivers afatinib and paclitaxel (PTX) is developed for treatment of EGFR TKIs resistant NSCLC. In this system, afatinib is loaded in stearic acid-based solid lipid nanoparticles, then these nanoparticles and PTX are loaded in poly-lactide- co -glycolide-based porous microspheres. These inhaled microspheres systems are characterized including geometric particle size, drug encapsulation efficiency, morphology by scanning electron microscopy, specific surface area, in vitro drug release, and aerodynamic particle size. Cell experiments indicate that afatinib and PTX have a synergistic effect and the codelivery system shows a superior treatment effect in drug-resistant NSCLC cells. The biocompatibility, pharmacokinetic, and tissue distribution experiments in Sprague–Dawley rats show that afatinib and PTX in the system can maintain 96 h of high lung concentration but low concentration in other tissues, with acceptable safety. These results demonstrate that this system may be a prospective delivery strategy for drug combination treatment in cancers developing resistance, especially drug-resistant lung cancer.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
肺癌研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Xiang Han,Feiyang Wang,Yuzhuo Ma,Xuerong Lv,Kewei Zhang,Yue Wang,Ke Yan,Youmin Mei,Xiaoqian Wang
Traditional fibrous membranes employed in guided tissue regeneration (GTR) in the treatment of periodontitis have limitations of bioactive and immunomodulatory properties. We fabricated a novel nTPG/PLGA/PCL fibrous membrane by electrospinning which exhibit excellent hydrophilicity, mechanical properties and biocompatibility. In addition, we investigated its regulatory effect on polarization of macrophages and facilitating the regeneration of periodontal tissue both in vivo and in vitro. These findings showed the 0.5%TPG/PLGA/PCL may inhibit the polarization of RAW 264.7 into M1 phenotype by suppressing the PI3K/AKT and NF-κB signaling pathways. Furthermore, it directly up-regulated the expression of cementoblastic differentiation markers (CEMP-1 and CAP) in periodontal ligament stem cells (hPDLSCs), and indirectly up-regulated the expression of cementoblastic (CEMP-1 and CAP) and osteoblastic (ALP, RUNX2, COL-1, and OCN) differentiation markers by inhibiting the polarization of M1 macrophage. Upon implantation into a periodontal bone defect rats model, histological assessment revealed that the 0.5%TPG/PLGA/PCL membrane could regenerate oriented collagen fibers and structurally intact epithelium. Micro-CT (BV/TV) and the expression of immunohistochemical markers (OCN, RUNX-2, COL-1, and BMP-2) ultimately exhibited satisfactory regeneration of alveolar bone, periodontal ligament. Overall, 0.5%TPG/PLGA/PCL did not only directly promote osteogenic effects on hPDLSCs, but also indirectly facilitated cementoblastic and osteogenic differentiation through its immunomodulatory effects on macrophages. These findings provide a novel perspective for the development of materials for periodontal tissue regeneration.
研究领域:
牙科材料
·
组织工程
·
免疫学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Huang Yaxian,Wu Jinyan,Zhan Chi,Liu Rong,Zhou Zhaocai,Huang Xin,Tian Yaguang,Lin Zhengmei,Song Zhi
The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.
研究领域:
牙科学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 8
·1-12
·
IF 3.3
Jiang Wenjing,Gao Xiangjun,Wang Qiuli,Chen Yang,Li Dan,Zhang Xiaoyan,Yang Xinggang
The existing exenatide microspheres have the problem of burst release in the early stage, and minimal release in the middle stage which makes it difficult to achieve effective blood drug concentration (platform period). In this study, the modified exenatide microspheres were constructed to address the aforementioned issues. Poly(D,L-lactic-co-glycolic acid) (PLGA) and triblock copolymer with sol-gel conversion characteristics (PLGA-PEG-PLGA gel) were introduced as carriers to prepare microspheres. The hot gel characteristics and hydrophilicity of PLGA-PEG-PLGA gel were utilized to decline the burst release and shorten the platform period. Simultaneously, zinc acetate and exenatide were combined to generate an insoluble complex to further reduce the burst release. Herein, we prepared three types of exenatide microspheres using the solvent evaporation method and investigated their characterization as well as in vitro and in vivo release. According to the experimental findings, the modified exenatide microspheres, i.e., PLGA-PEG-PLGA gel and PLGA co-loaded zinc-exenatide insoluble complex microspheres (Zn-EXT-Gel-MS), had smooth and rounded surfaces, with a particle size of 24.7 μm, and the encapsulation rate reached 89.43%. And it was released for 40 days in vitro , behaving better than the other two microspheres in terms of release behavior. When this product was administered subcutaneously to rats, it produced a comparatively constant plasma exenatide concentration that lasted for 24 days and superior bioavailability than the exenatide microspheres (EXT-MS). The creation of modified exenatide microspheres may serve as a heuristic method for other long-acting medications. Graphical Abstract Schematic diagram of the synthesis process and release curves of three types of exenatide microspheres in vitro and in vivo
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 11
·期 4
·826-836
·
IF 7.571
Enhui Qiu,Yan Gong,Jieran Yao,Jinqing Lai,Zhihua Liu,Da-Peng Yang,Li Shen,Xiangrong Chen
Injured bone regeneration requires a systemically and carefully orchestrated series of events involving inflammation, angiogenesis, and osteogenesis. Thus, we designed a multifunctional cell-supporting and drug-retarding dual-pore system: cell-free fat extract (Ceffe)-mesoporous silica nanoparticle (MSN)@poly(lactic-co-glycolic acid) (PLGA) (Ceffe-MSN@PLGA) to mimic the developmental spatial structure, the microenvironment of bone regeneration and integration during injured bone regeneration. In this system, a macroporous scaffold (pore size 200–250 μm) of PLGA is combined with mesoporous MSN (pore size 2–50 nm), aiming at realizing the slow release of Ceffe. Besides, PLGA and MSN are used to recruit the temporary support of cells that are able to degrade simultaneously with bone regeneration and provide space for bone tissue regeneration. And the Ceffe isolated from fresh human adipose tissue has a therapeutic effect in regulating the important functions of early inflammatory cell transformation, neovascularization and eventual osteogenic differentiation. Our results suggest that the mesoporous and macroporous Ceffe-MSN@PLGA system represents a promising strategy to better fit the regeneration of injured bone tissue.
研究领域:
组织工程
·
生物材料
·
再生医学
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2026
·
IF 6.9
Yuan Hao,Zhang Bingwen,Sun Wen,Liu Haofan,Hu Liandong
In this study, celecoxib (CXB) microspheres (CM) and ropivacaine (RPV) microspheres (RM) were prepared respectively. A poly (D, L-lactide-co-glycolide)-block-poly (ethylene glycol)-block-poly (D, L-lactide-co-glycolide) (PLGA–PEG–PLGA, PPP) was synthesized by copolymerizing glycolide and lactide with polyethylene glycol. CM, RM, and hydroxyapatite (HA) were then incorporated into PPP solution to construct the microsphere–hydrogel system (CRMH hydrogels). CM, RM, and CRMH were systematically characterized in terms of morphology, physicochemical properties, pH-buffering capacity, and degradation behavior. The pH-dependent drug release and release kinetics of the individual CM, RM and the CRMH hydrogels were also investigated. In vitro release studies demonstrated that CRMH hydrogels provided coordinated, sustained release of CXB and RPV at pH 6.2. In a rabbit osteoarthritis (OA) model, intra-articular (IA) administration of CRMH hydrogels achieved sustained drug retention and release within the joint cavity, and effectively promoted articular cartilage repair. Overall, the CRMH hydrogels showed promising synergistic therapeutic potential for OA.
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2026
·Vol. 16
·期 23
·20895-20907
·
IF 6.1
Xiaolong Xu,Yuze Zhou,Junhao Chen,Lujing Fei,Min Qi
The treatment of malignant melanoma, an aggressive skin cancer with high recurrence and metastatic potential, often presents challenges due to systemic toxicity and multidrug resistance in current therapies. In this study, we develop a localized therapeutic platform by integrating methotrexate–manganese (MTX–Mn) coordination nanoparticles into a thermosensitive PLGA–PEG–PLGA (PPP) hydrogel to achieve sustained and site-specific drug delivery for melanoma treatment. MTX–Mn nanoparticles were synthesized through coordination-driven self-assembly and comprehensively characterized by FTIR, 1H NMR, TEM, EDS, and zeta potential analyses, confirming successful coordination and uniform nanoscale features. In vitro experiments demonstrated that MTX–Mn significantly inhibited melanoma cell proliferation and migration. Flow cytometry further revealed that MTX–Mn induced pronounced G0/G1 cell-cycle arrest and effectively promoted apoptosis, which was confirmed by TUNEL staining. Mechanistic investigations indicated that MTX–Mn triggered severe mitochondrial dysfunction, including ultrastructural damage, elevated mitochondrial ROS generation, and collapse of mitochondrial membrane potential (JC-1), suggesting a mitochondria-associated antitumor mechanism. In vivo, peritumoral administration of PPP/MTX–Mn markedly suppressed tumor growth in a melanoma-bearing mouse model, reduced the tumor burden, and significantly decreased Ki-67 expression. Histological evaluation of major organs by H&E staining revealed no obvious pathological abnormalities, supporting good in vivo biosafety. Overall, this MTX–Mn-loaded thermosensitive hydrogel provides a promising strategy for effective and safe localized melanoma therapy.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES
·
2019
·
IF 1.463
Qi Wang,Mengfei Shen,Wenjing Li,Wanwan Li,Fang Zhang
Pesticides are biological or chemical substances used to manage pests and diseases. Encapsulation of pesticides in biodegradable carriers creates a slow-release system that can improve water dispersibility and prolong residual activity. We prepared two kinds of poly (lactic-co-glycolic acid)(PLGA) nanoparticles (NPs) with polyvinyl alcohol (PVA) and sodium dodecyl sulfate (SDS) surfactants. These were used to encapsulate the fungicide fluazinam (Flu) against Rhizoctonia solani using the Shirasu Porous Glass (SPG) membrane emulsification method. Both nanoparticles had uniform spherical shapes with average diameters of 314.13 nm (SDS) and 612.80 nm (PVA). The slow-release microspheres had excellent sustained-release properties, resistance to UV degradation, storage stability, leaf surface coverage and antifungal efficacy compared to the commercial formulation.
研究领域:
农业科学
·
材料科学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 3
·376
·
IF 5.5
Yuxing Zhang,Xixi Zou,Qiran Du,Xiaotao Dong,Uday Kumar Chinta,Ruyue Yu,Fei Wu,Tuo Jin
Objectives: Thermo-gelling hydrophilic polymers like PLGA–PEG–PLGA are known as injectable sustained-release depots for biologics, but they face challenges due to the occurrence of severe burst release. This study aimed to develop a strategy to avoid the initial burst release by pre-encapsulating proteins in polysaccharide microparticles through an aqueous–aqueous emulsion mechanism, thereby enhancing therapeutic retention and linear release kinetics.Methods: Five model proteins (G-CSF, GM-CSF, IGF-1, FVIII, BSA) were encapsulated in dextran microparticles, using an organic solvent-free aqueous–aqueous emulsion method. These particles were dispersed in a 23% (w/w) PLGA–PEG–PLGA solution and injected into a 37 °C release buffer to form a gel depot. The in vitro release profiles were quantified using ELISA and MicroBCA assays over 9–42 days. The bioactivity of the proteins was validated using cell proliferation assays (NFS-60, TF-1, MCF-7) and chromogenic kits. The in vivo pharmacokinetics of the FVIII-loaded formulations were evaluated in Sprague–Dawley rats (n = 5/group) over 28 days.Results: Protein-loaded dextran particles retained their structural integrity within the hydrogel and exhibited minimal burst release (≤5% within 30 min vs. >25% for free proteins). Sustained near-linear release profiles were observed for all the proteins, with complete release by day 9 (G-CSF, GM-CSF, BSA) or day 42 (FVIII). Rats administered with the thermal gel with FVIII–dextran particles showed a significantly lower peak plasma concentration (Cmax: 88.25 ± 30.21 vs. 132.63 ± 66.67 ng/mL) and prolonged therapeutic coverage (>18 days vs. 15 days) compared to those administered with the thermal gel with the FVIII solution. The bioactivity of the released proteins remained at ≥90% of the native forms.Conclusions: Pre-encapsulation in dextran microparticles effectively mitigates burst release from thermosensitive hydrogels, while preserving protein functionality.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
·
蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Qinghui Wang,Xiaoyu Ding,Yuhui Wang,Qian Du,Tianguo Xu,Bin Du,Hanchun Yao
Tumor pH detection and pH value change monitoring have been of great interest in the field of nanomedicine . In this study, a pH-sensitive near-infrared fluorescence probe SiRB (Si-rhodamine and Boronic acid group) was synthesized by introducing a boronic acid group into the silicon rhodamine structure. ICG (Indocyanine green) as the fluorescence internal standard and SiRB were loaded into PLGA (poly lactic- co -glycolic acid) to form PLGA-SiRB-ICG nanoparticle . The experiments showed that the size of the nanoparticle was about 90 nm, which can reach tumor passively by enhancing permeability and retention effect. PLGA in the acidic environment will accelerate the release of cleavage, and the fluorescence ratio of the two probes can reflect the specific pH value in the tumor. The results indicated that the nanoparticle could quantitatively measure the pH value of the tumor site, which is expected to be used in tumor research and treatment.
研究领域:
纳米医学
·
生物化学
·
肿瘤学
✓ 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）