ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Shan Wang,Yabing Hua,Jijun Yu,Xudong Dai,Yuhua Ran,Wenpeng Zhang,Yanan Zhai,Zhiping Li,Xiaomei Zhuang,Jing Gao
Thorough understanding and accurate prediction of in vivo drug release are essential for developing long-acting microsphere systems. However, the fate of microspheres after prolonged tissue residence and the regulatory role of physiological factors remain unclear, hindering elucidation of release mechanisms. Herein, the dynamic evolution of microsphere depots and associated microenvironmental changes were studied. Beyond poly(lactic-co-glycolic acid) (PLGA) and API effects, microsphere depot behavior is partly regulated by conserved biological processes, with skeletal muscle and subcutaneous tissue employing distinct adaptive strategies to restore homeostasis. Using these insights, we developed the in vivo release predictive models (IVRPMs) that establish a true IVIVC for naltrexone PLGA microspheres. The IVRPMs demonstrated broad applicability across microspheres with different APIs and PLGA types, and showed promising translational potential in beagle and human studies. This study shifts the research paradigm from “material-dominated release” to “organism-material coevolution”, addressing a key question in depot formulation fate.
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DOI
高影响因子
International Journal of Nanomedicine
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2021
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IF 6.4
Qiangqiang Wang,Xiaoke Sun,Xin Huang,Jianmei Huang,Muhammad Waqqas Hasan,RuoFeng Yan,Lixin Xu,Xiaokai Song,Xiangrui Li
Background Hepatocellular carcinoma-associated antigen 59 (HCA59) from excretory/secretory products of Haemonchus contortus is known to have the ability to modulate the functions of host cells. However, its immunogenicities using different nanoparticles adjuvants remain poorly understood. Purpose The study aimed to select an efficient nanoparticle antigen delivery system, which could enhance the immune responses of Haemonchus contortus HCA59 in mice. Methods Here, the immune responses induced by the recombinant protein of HCA59 (rHCA59) with poly-D,L-lactide-co-glycolide (PLGA) nanoparticles, Chitosan nanoparticles, mixture of PLGA and Chitosan nanoparticles (rHCA59-Chitosan-PLGA), and Freund’s complete adjuvant were observed, respectively, in mice. Cytokine and antibody levels induced by different groups were detected by ELISA assay. The effects of lymphocyte proliferations on different groups were examined using CCK-8 kit. Phenotypes of T cells and dendritic cells were analyzed by flow cytometry. Results On day 14 post vaccination, levels of IgM, IgG1, IgG2a, IFN-γ, IL-4, and IL-17 were significantly increased in the groups immunized with rHCA59 encapsulated with nanoparticles. After mice were vaccinated with rHCA59 loaded with Chitosan/PLGA nanoparticles, lymphocytes proliferated significantly. Additionally, the percentages of CD4 + T cells (CD3 + CD4 + ), CD8 + T cells (CD3 + CD8 + ), and dendritic cells (CD11c + CD83 + , CD11c + CD86 + ) were obviously up-regulated in the mice immunized with nanoparticles, especially in the rHCA59-Chitosan-PLGA antigen delivery system group. Conclusion The findings of this research demonstrated that rHCA59-Chitosan-PLGA antigen delivery system could induce higher immune responses in mice model and indicated that rHCA59 might be a good candidate molecule to develop nanovaccines against Haemonchus contortus in future study.
研究领域:
寄生虫学
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免疫学
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疫苗研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Chi Zhang,Li Jun,Yuxiang Gao,Le Guo,Jiayi Ding,Lijun Zhu,Zhong Du,Jiabao Xiong,Xueliang Zhang,Wenbao Zhang,Biao Dong,Nuernisha Alifu
Alveolar echinococcosis (AE) is a serious parasitic infectious disease that is highly invasive and destructive to the liver and has a high mortality rate. However, currently, there is no effective targeted imaging and treatment method for the precise detection and therapy of AE. We proposed a new two-step targeting strategy (TSTS) for AE based on poly(lactic-co-glycolic acid) (PLGA). We designed and constructed a novel type of ICG@PLGA@Lips nanoprobe with integrated imaging and treatment properties. First, we used the characteristics of PLGA gluconeogenic raw material to target the liver during blood circulation. Then, we utilized the characteristics of PLGA specifically penetrating the AE shell to achieve specific identification of AE in the liver. Under 808 nm laser excitation, ICG@PLGA@Lips effectively achieved accurate imaging of AE based on near-infrared II (NIR-II, 900–1700 nm) fluorescence imaging methods and achieved AE treatment through PDT effects. PLGA improved the optical properties of ICG, while liposomes further improved the biocompatibility of the nanoprobe. As ICG@PLGA@Lips showed strong NIR-II fluorescence emission and good biocompatibility, ICG@PLGA@Lips showed advantages in the specific fluorescence navigation of AE surgical resection lesions. Thus, with the assistance of ICG@PLGA@Lips, we achieved precise targeted and real-time NIR-II fluorescence imaging of AE for the first time. We successfully obtained in vivo NIR-II fluorescence imaging-guided photodynamic/surgical therapy of AE. This TSTS-based AE imaging and treatment exploration provided a new strategy for accurate imaging and treatment of early AE, which is expected to significantly improve the prognosis of patients.
研究领域:
医学成像
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诊疗学
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纳米技术
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寄生虫学
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外科手术
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光子学
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产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
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2021
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IF 9.078
Xiyu Li,Qin Zou,Jiawei Wei,Wei Li
Scaffold degradation regulation has become the key aspects in promoting bone regeneration and reconstruction. In the study, a novel stepwise-degraded PLGA/PCL/HA:Yb/Ho/Zn (PPHZ) scaffold was designed to compare with the fast-degradable PLGA/HA:Yb/Ho/Zn (PLHZ) scaffold to investigate the effects of scaffold degradation regulation on osteogenesis and to trace the scaffold degradation process. Micro-CT reconstruction, confocal fluorescence imaging, and histological sections were used for the analyses of the harvested animal samples, which demonstrated that the degradation regulated stepwise-degraded PPHZ scaffold maintaining higher mechanical strength and longer scaffold integrity is more advantageous for in vivo osteogenesis than the fast-degradable PLHZ scaffold. Meanwhile, the multifunctional HZ particles would help the anti-infection and tracking the distribution during scaffold degradation. The PPHZ scaffold may benefit future repair of anti-infective bone defects and in vivo multimodal tracking.
研究领域:
生物医学工程
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组织工程
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生物材料科学
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骨科研究
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2015
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IF 6.723
Jianyong Sheng,Limei Han,Jing Qin,Ge Ru,Ruixiang Li,Lihong Wu,Dongqi Cui,Pei Yang,Yuwei He,Jianxin Wang
Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded N-trimethyl chitosan chloride (TMC)-coated polylactide-co-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6 ± 7.2 nm), ζ-potential (45.2 ± 4.6 mV), insulin-loading capacity (7.8 ± 0.5%) and encapsulation efficiency (47.0 ± 2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics.
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2020
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IF 2.734
Bo Yu,Ying Pu,Jun Liu,Jie Liao,Ke Chen,Jiani Zhang,Wen Zhong,Yalan Hu,Xue-Qiang Wang,Bo Liu,Huixia Liu,Weihong Tan
Targeted delivery of antiobesity drugs to adipocytes presents a novel strategy for obesity treatment. The 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue is an attractive therapeutic target of obesity. Emodin (EMO) has been proven to be a potent and selective inhibitor of 11β-HSD1, but it frequently exerts low bioavailability owing to its poor water solubility and lack of tissue specificity. In this work, we conjugated a nanoscale drug delivery polymer with Adipo8 (Ap), a DNA aptamer with high affinity to mature white adipocytes, as a targeting modality that enabled selective delivery of emodin to adipocytes. Emodin-loaded PEG-PLGA nanoparticles (EMO-NPs) were formulated by a modified oil-in-water (O/W) emulsion solvent evaporation method, and Ap was covalently bound to the NP surface via the EDC/NHS method. The NPs were structurally investigated by TEM imaging, DLS and UV-VIS spectroscopy. The resulting aptamer-conjugated, emodin-loaded nanoparticles (Ap-EMO-NPs) had a spherical shape and an average particle size of 146.7 ± 27.85 nm with a drug loading of around 6.8% and a sustained-release property. Confocal microscopy and flow cytometry demonstrated a significant increase in the internalization of Ap-EMO-NP in differentiated 3T3-L1 cells compared to EMO-NP functionalized with nonspecific aptamer. As confirmed by Oil Red O coloring, the Ap-EMO-NPs reduced lipid stacking in 3T3-L1 adipocytes in a sustained-release and dose-dependent manner. The results indicated that Adipo8-functionalized PEG-PLGA NPs could be a potential targeted therapeutic delivery vehicle for obesity treatment.
研究领域:
药理学
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生物医学工程
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Yunchun Zhao,Caihong Zheng,Li Zhang,Yue Chen,Yiqing Ye,Mengdan Zhao
Biodegradable and biocompatible poly( d,l -lactic- co -glycolic acid) (PLGA)was conjugated to the 5′-thiol end of signal transducer and activator of transcription 3 (STAT3) small interfering RNA (STAT3–siRNA) via a disulfide bond. In aqueous environments, these siRNA–PLGA conjugates can spontaneously form core/shell type spherical micelles with a particle size of about 200 nm. A biodegradable, low molecular weight cationic polymer, chitosan oligosaccharide (CSO), was added to the siRNA–PLGA micelles at different nitrogen to phosphate (N/P) ratios to form stable, spherical siRNA–PLGA/CSO micelles with sizes of 150–180 nm. The siRNA–PLGA/CSO micelles were produced via ionic complexation between negatively charged siRNA and positively charged CSO on the outer shell of the micelles. The siRNA–PLGA/CSO micelles exhibited superior cellular uptake and STAT3 gene silencing efficiency in SKOV3 ovarian cancer cells when compared with siRNA/CSO complexes at the same N/P ratios with no significant differences with lipofectamine 2000. Furthermore, the siRNA–PLGA/CSO micelles showed that the efficiencies of cellular uptake and STAT3 gene silencing gradually increased with increasing N/P ratios. The siRNA–PLGA/CSO micelles also inhibited the growth of SKOV3 cells, as well as, promoted apoptosis of the cells. These results indicate that siRNA–PLGA/CSO micelles can be utilized as a novel and efficient siRNA carrier to treat a variety of diseases.
研究领域:
癌症研究
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药学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2019
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IF 4.959
Zetao Wang,Ruiming Liang,Xianfang Jiang,Jiali Xie,Peian Cai,Haimin Chen,Xintang Zhan,Danqing Lei,Jinmin Zhao,Li Zheng
Nanofibers as niche-biomimetic scaffolds hold promise in guided bone regeneration (GBR). Here we fabricated poly (lactic- co -glycolic acid) (PLGA)/poly(caprolactone) (PCL)-doped octacalcium phosphate (OCP) nanofiber membranes via electrospinning and investigated the osteogenic behavior of marrow mesenchymal stem cells (MSCs) on the membranes. By adjusting different ratio of OCP to PLGA/PCL, three hybrid stents including PLGA/PCL, PLGA/PCL/2 wt%OCP, PLGA/PCL/4wt%OCP were successfully prepared. The PLGA/PCL/OCP membranes showed a decrease in fiber diameter compared with PLGA/PCL, leading to enhanced mechanical strength. In-vitro studies showed that PLGA/PCL/OCP membranes better supported cell adhesion, spreading and proliferation than PLGA/PCL. The incorporation of OCP via electrospinning also endowed the membranes with osteoinductive capacity, as evidenced by activation of ALP activity, increased gene expression of bone specific markers (such as Runx2 , ALP , Col 1a1 , OPN , OCN , BMP2 ), and mineral nodules formation compared to PLGA/PCL. Comparatively, PLGA/PCL/4wt%OCP showed better mechanical and biological performance than PLGA/PCL/2 wt%OCP, demonstrating the role of OCP in nanofiber membranes. Thus, the electrospun PLGA/PCL/OCP nanofiber membranes can be potentially developed as a promising hybrid stent for GBR.
研究领域:
生物材料
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组织工程
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干细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2026
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IF 5.8
Chunlian Liu,Siwen Wang,Haifan Yu,Kai Duo,Chunyu Wang,Jing Jiang,Lin Li
Parkinson’s disease (PD), the second leading cause of neurodegenerative disease worldwide, severely impairs the quality of life for the elderly. While current clinical treatments can alleviate symptoms, they fail to halt the progressive death of neurons, making the disease progression irreversible. This treatment bottleneck is largely attributed to the inability to effectively alleviate the “energy metabolism crisis” of dopaminergic neurons. Against this backdrop, piperine (Pip) has shown some neuroprotective potential, but its poor water solubility and inability to penetrate the blood–brain barrier (BBB) limit its application. This study aimed to develop RVG29 peptide-modified erythrocyte membrane biomimetic nanoparticles (RVG29-RM@Pip NPs) to address delivery challenges and explore metabolic intervention strategies. This system uses PLGA to load piperine, achieving immune escape and active brain targeting through biomimetic camouflage and RVG29 guidance. In vitro and in vivo experiments confirmed that these nanoparticles can efficiently penetrate the BBB, restore mitochondrial membrane potential, scavenge reactive oxygen species, and significantly improve motor dysfunction and neuronal loss in MPTP mice. Mechanistically, it remodels neuronal glycolysis and respiratory chain function by synergistically upregulating GLUT1, the rate-limiting enzyme PGK1, and mitochondrial complex I, restoring energy homeostasis and inhibiting apoptosis. This study not only constructed a brain-targeted delivery system but also revealed a mechanism and candidate approach for treating PD through metabolic remodeling.
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产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
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2026
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IF 6
Xiaoming Li,Kun Li,Siqi Liu,Can Yang,Shuo Yang,Jimin Guo,Jianjun Zhang
Bone defect repair is a precisely choreographed, multiphase cascade that imposes temporally distinct demands on the implanted scaffold. The critical challenge is to create an implant that sustains potent anti-inflammatory and osteogenic signals while eroding at a pace matched to the more than 6-month remodeling timeline. Here, we reported ultralong-acting microspheres that meet this requirement across the entire regeneration program. By synergistically integrating polydopamine-coated poly(lactic-co-glycolic acid) (PLGA–PDA) microspheres with nanohydroxyapatite (nHAP) and mesenchymal stem cell-derived exosomes (Exo), the nHAP/PLGA–PDA@Exo system reconciled extended degradation with durable bioactivity. nHAP neutralized acidic PLGA byproducts to decelerate matrix erosion and release calcium ions, amplifing osteoinduction. Exo modulated inflammation, promoted angiogenesis, and enhanced tissue regeneration, while the PDA coating maximized Exo loading and orchestrated its sustained release. The microspheres released bioactive Exo for more than 3 weeks and retained mechanical integrity for over 6 weeks, thereby furnishing continuous immunomodulation, robust osteogenesis, and time-matched structural support. By dynamically coordinating immune modulation and bone formation throughout the inflammatory, reparative, and remodeling phases, nHAP/PLGA–PDA@Exo offered a clinically translatable strategy for bone defects.
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2026
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IF 8.7
Zhang Junjiang,Chang Yuqi,Zhou Yiwen,Zhou Yang,Li Jiayin,Wang Feng,Zhou Zhimin,Sui Lei,Li Yanjing
Maxillofacial bone defects present a major challenge in clinical practice. Bone graft and bone tissue engineering are limited by various side effects and potential risks, while local drug delivery is regarded as a convenient and efficient strategy for bone repair and regeneration. However, for bone tissue regeneration, drug delivery system should not only release osteogenic drugs, but also possess an appropriate morphology to provide structural support for cell proliferation and differentiation. Polymeric non-spherical counterparts may offer new osteogenic properties through altered cellular interactions, biodistribution, and immune responses, compared with spherical drug carriers. Poly(lactic-co-glycolic) acid (PLGA) has been widely used to prepare various drug carriers due to its excellent biocompatibility and controllable biodegradation. Shape regulation, surface modification, and drug incorporation are effective approaches to impart distinct functions to PLGA particles for various biomedical applications. However, PLGA has inherent limitations, including poor hydrophilicity, acidic degradation products, and a lack of functional ligands for cell attachment, which hinder its effectiveness in bone regeneration. To solve these problems, natural proteins were utilized to improve the bone/cartilage regeneration of polymeric particles/scaffolds through surface modification or physical complex due to their excellent biocompatibility and biodegradability.In this study, we successfully developed simvastatin (SIM)-loaded disc-shape PLGA microparticles with coarse surface (dPLGA) using W1/O/W2 followed by silk fibroin (SF) coating for hydrophilicity and biocompatibility improvement. In vitro and in vivo experiments revealed that SF-modified SIM-loaded dPLGA (SF-SIM@dPLGA) significantly promotes the osteogenic differentiation of stem cells and bone regeneration in cranial bone defects, indicating the superior osteoconductive and osteoinductive advantages arising from the physical morphology of particles and chemical effect. Additionally, SF-SIM@dPLGA demonstrated improved tissue adhesion and hemostatic ability. This novel PLGA non-spherical particle-based local delivery system provides a feasible strategy for practical maxillofacial bone repair due to the simple preparation procedures and enhanced bone regeneration performance.
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产品关联
DOI
PubMed
高影响因子
Animal Models and Experimental Medicine
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2026
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IF 3.3
Yanyu Li,Jingting Luo,Shitao Zou,Xin Zhang,Zhen Wang,Ziwen Jiang,Jingjie Wang,Zhaoxia Liu,Zhimin Zhou
Background Intravaginal drug administration is the most promising strategy for treating vaginal infections to protect women's health, such as vulvovaginal candidiasis (VVC). However, conventional vaginal formulations in the clinic face challenges such as drug leakage and low bioavailability due to the mucus barrier and vaginal self-cleaning behavior. To address these limitations, we designed and optimized clotrimazole-loaded PLGA non-spherical microparticles (CPNMs) for vaginal drug delivery. Methods CPNMs and clotrimazole-loaded PLGA porous microspheres (CPMs) were prepared by the double emulsion-solvent evaporation method. The physicochemical features and in vitro drug release kinetics were characterized, and the effect of shape on drug delivery were also investigated. After intravaginal administration of CPMs and CPNMs, the pharmacokinetics and biocompatibility in the vagina of mice were studied. Results Both CPMs and CPNMs exhibited sustained release features in vitro. Initially, there was a rapid release within the first 24 h and the cumulative release of CPMs and CPNMs was 46.55% and 56.89% over 7 days, respectively. Compared to CPMs, CPNMs demonstrated an extended drug release in vivo, maintaining a residence duration of at least 72 h, which was beneficial for clotrimazole delivery at a high concentration in the vagina of mice. Histological evaluation demonstrated the low cytotoxicity and good biocompatibility of CPNMs, with no obvious damage to vaginal epithelial cells. Conclusion This vaginal drug delivery system offers potential applications for managing VVC, along with other health concerns in women.
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）