INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
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IF 6
Xia Yin,Bin Chen,Yan Qing Wang,Yan Yan,Qian Ding,Suguro Rinkiko,Yi Chun Zhu,Yi Zhun Zhu
Efficient encapsulating of highly hydrophilic low-molecular-weight compound within poly (D, L-lactic-co-glycolic acid) (PLGA) to obtain microspheres with both excellent drug loading capacity (DL) and encapsulation efficiency (EE) was substantially challenging. This study specifically aimed to enhance both the DL and EE of this hydrophilic low-molecular-weight compound S-propargyl-cysteine (SPRC) while extending its release duration through implementation of the solvent-induced phase separation (SIPS) methodology. S-propargyl-cysteine (SPRC)-loaded PLGA microspheres (SP-MSs) were fabricated using conventional emulsion solvent evaporation techniques (W/O/W and S/O/W) and compared with those prepared via SIPS. The influences of various preparation techniques on critical pharmaceutical properties of sustained-release SP-MSs, including drug loading capacity, encapsulation efficiency, in vitro release profiles, surface-localized drug content, crystal state of SPRC, and microstructural characteristics were also systematically investigated. Microspheres sythesized through SIPS demonstrated a remarkable enhancement in DL, increasing from 0.90% to 9.91%, with the corresponding EE improving dramatically from 17.8% to 99.2%. Furthermore, the SIPS approach effectively mitigated the initial burst release phenomenon commonly observed in polymeric microsphere formulations. In vivo pharmacokinetic studies in Sprague-Dawley rats confirmed the sustained-release profile of the optimized formulation, maintaining stable plasma concentrations for an extended period of seven days. These findings establish SIPS as a superior methodology for encapsulating SPRC within PLGA microspheres, effectively addressing dual challenges of low DL and EE. This investigation provides significant methodological insights for the effective encapsulation of hydrophilic low-molecular-weight therapeutic agents within PLGA-based delivery systems, offering a promising strategy for achieving prolonged sustained-release both in vitro and in vivo . Solvent-induced phase separation was employed to encapsulate highly hydrophilic S-propargyl-cysteine (SPRC) within injectable PLGA microspheres to (i) maximize EE and DL, (ii) suppress the initial burst, and (iii) achieve prolonged, controlled release of SPRC for 7 days both in vitro and in vivo . Download: Download high-res image (93KB) Download: Download full-size image
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
·
IF 2.2
Chang Luo,Cheng Kang,Shi Qiu,Weiming Wang,Yiyi Lou,Xiaofei Wang,Ting Zhu
Biodegradable scaffolds have significant potential for directed tissue regeneration in craniofacial and oral applications and bone regeneration. We designed an innovative cerium-altered/collagen-clacked polycaprolactone/poly-lactic-co-glycolic acid (PC/PL) electrospun scaffolds (PC/PL-PD-Ce-CL) to address the deficiencies of existing scaffold materials regarding osteogenic and antimicrobial characteristics. Novel scaffolds were developed by electrospinning a fundamental PCL/PLGA matrix, impregnating in situ reduction with cerium nanoparticles (CeNPs), applying a polydopamine coating, and clacking with collagen. The mechanical tests and scanning electron microscope demonstrated that the distinctive NSs preserved their tensile strength and elasticity modulus post-modification. The cell proliferation CCK-8 assay indicated that the PC/PL-PD-Ce-CL NSs exhibited a superior MG63 cell proliferation and cell adhesion ratio compared to the rest of the NSs. The alkaline phosphatase (ALP) activity and the expression levels of BMP2 and RUNX2 in MG63 cells cultivated on PC/PL-PD-Ce-CL NSs for 7 and 14 days were considerably elevated compared to the controls. The PC/PL-PD-Ce-CL and PC/PL-PD-Ce NSs exhibited a broader antibacterial zone compared to the control NSs, and bacterial fluorescence diminished on the Ce-altered NSs of incubation with S. mutans and S. aureus . Our innovative PC/PL-PD-Ce-CL NSs improved cytocompatibility, osteogenesis, and antibacterial capabilities, demonstrating their promising therapeutic applications for orofacial treatment.
研究领域:
生物材料学
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组织工程学
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口腔医学
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International Journal of Nanomedicine
·
2023
·
IF 8
Liping Zhang,Yuan Xu,Wenjuan Cao,Shibao Xie,Lu Wen,Gang Chen
Background The round window membrane (RWM) functions as the primary biological barrier for therapeutic agents in the inner ear via local application. Previous studies on inner ear nano-drug delivery systems mostly focused on their pharmacokinetics and distribution in the inner ear, but seldom on the interaction with the RWM. Clarifying the transport mechanism of nanoparticulate carriers across RWM will shed more light on the optimum design of nano-drug delivery systems intended for meeting demands for their clinical application.Methods The poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) encapsulating coumarin-6 were prepared by emulsifying solvent evaporation method. We utilized confocal laser scanning microscope (CLSM) in combination with transmission electron microscope to investigate the transport pathway of PLGA NPs in the RWM. Simultaneously, the concentration and time dependence of NPs across the RWM were also determined. The endocytic mechanism of NPs through this membrane interface was classically analyzed by means of various endocytic inhibitors. The intracellular location of NPs into lysosomes was evaluated using CLSM scanning microscope colocalization analysis. The Golgi-related inhibitors were employed to probe into the function of Golgi and endoplasmic reticulum (ER) in the discharge of NPs out of cells.Results PLGA NPs were herein transported through the RWM of a sandwich-like structure into the perilymph via the transcellular pathway. NPs were internalized predominantly via macropinocytosis and caveolin-mediated endocytic pathways. After being internalized, the endocytosed cargos were entrapped within the lysosomal compartments and/or the endoplasmic reticulum/Golgi apparatus which mediated the exocytotic release of NPs.Conclusion For the first time, we showed the translocation itinerary of NPs in RWM, providing a guideline for the rational fabrication of inner ear nanoparticulate carriers with better therapeutic effects.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 24
·期 1
·390
·
IF 6.208
Haozhe Cheng,Qian Guo,Hongjian Zhao,Kun Liu,Honglei Kang,Fang Gao,Jianfeng Guo,Xi Yuan,Shuang Hu,Feng Li,Qin Yang,Zhong Fang
Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.Keywords:drug delivery;hydrogel;intervertebral disc degeneration;immune regulation;kartogenin
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Ningchao Luo,Lisha Ma,Ninghui Ma,Jiale Wei,Hongyan Zhang,Wanyu Jin,Yujie Li,Jingbin Shi,Yang Xiong
Triple negative breast cancer (TNBC) represents a heterogeneous subtype of breast cancer characterized by an unfavorable prognosis due to its aggressive biology. Cancer-associated adipocytes (CAAs) play an active role in tumor development, invasion and metastasis, and response to treatment by secreting various cytokines. CAAs secrete CCL2 and ADPN which significantly affect the efficacy of aPD-1 in treating breast cancer. Our recent research has demonstrated that Hesperidin, a natural phenolic compound, significantly inhibits CCL2, elevates ADPN secreted by CAAs in vitro and in vivo, remodels the immune microenvironment, and potentiates the efficacy of aPD-1 in triple-negative breast cancer. We used Oil red staining, Bodipy 493/503 staining and quantitative real-time PCR to verify the formation of CAAs. ELISA was used to detect levels of CCL2, ADPN secreted by CAAs. Changes in the number of immune cells in mouse tumor tissues were detected using flow cytometry and immunofluorescence. Our data suggest that Hesperidin PLGA nanoparticles significantly reduced CCL2 and increased ADPN secreted by CAAs, which concurrently decreased the recruitment of M2 macrophages, Tregs and MDSCs while increased the infiltration of CD8 + T cells, M1 macrophages and DCs into tumor, thus significantly potentiated the efficacy of aPD-1 in vivo. This study provides a new combined strategy for the clinical treatment of triple-negative breast cancer by interfering with CCL2, ADPN secreted by CAAs to enhance the efficacy of immunotherapy.
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Journal of Materials Chemistry B
·
2024
·
IF 6.1
Jie Tan,Zecai Chen,Zhen Xu,Yafang Huang,Lei Qin,Yufeng Long,Jiayi Wu,Hantao Yang,Xuandu Chen,Weihong Yi,Ruiqiang Hang,Min Guan,Huaiyu Wang,Ang Gao,Dazhi Yang
The 3D printed scaffolds constructed from polymers have shown significant potential in the field of bone defect regeneration. However, the efficacy of these scaffolds can be markedly reduced in certain pathological conditions like diabetes, where the altered microenvironment complicates the integration of these polymers with the host tissue. In this study, the bioactivity of 3D-printed PLGA scaffold is augmented through integration of hydroxyapatite, icariin, and small intestine submucosa (SIS), a form of decellularized extracellular matrix (dECM). In vitro and in vivo studies demonstrate that this functionalized scaffold not only provides desirable immunoregulatory effect, but also facilitates angiogenesis and osteogenesis during the subsequent process. This functionalization approach holds significant promise in advancing the treatment of bone defects within the diabetic population, paving a step forward in the application of polymer-based 3D printing technologies in regenerative medicine.
研究领域:
再生医学
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生物医学工程
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组织工程
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糖尿病研究
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生物材料科学
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International Journal of Nanomedicine
·
2025
·
IF 6.5
A li mu Ke re mu,Maimaitiaili Abulikemu,Zhilin Liang,Abudurusuli Abulikemu,Aikebaier Tuxun
Background Given the limitations of traditional therapies, the treatment of infected bone defects (IBD) remains a great challenge. It is urgent to find a novel method that can simultaneously eradicate infection and promote new bone formation. With the increasing application of personalized scaffolds in orthopedics, novel biomaterials with both antibacterial and osteoinductive properties have provided a viable option for IBD treatment. Through the three-dimensional (3D) printing technology, we fabricated a poly(lactic-co-glycolic acid)(PLGA)/nano-hydroxyapatite (n-HA) composite scaffold grafted with the antibiotic vancomycin and loaded with the osteoinductive agent recombinant human bone morphogenic protein-2 (rhBMP-2) via polydopamine (DOPA) chemistry, whose therapeutic effects on IBD were determined.Methods After examining the hydrophilicity, surface chemical composition, mechanical properties, and drug release of the PLGA/n-HA, PLGA/n-HA/VAN, and PLGA/n-HA/VAN+DOPA/rhBMP-2 composite scaffolds, pre-osteoblast MC3T3-E1 cells were seeded onto the scaffold surface to assess the biocompatibility and osteoconductive properties of the scaffolds in vitro. For in vivo experiments, the composite scaffolds contaminated with Staphylococcus aureus were implanted into the defect sites of rabbit radius. After 12 weeks, micro-CT analysis, H&E and Masson staining, immunohistochemistry, and viable bacteria counting were conducted to compare the effects of three composite scaffolds on new bone formation and bone infection.Results The surface modification with DOPA/rhBMP-2 increased the hydrophilicity of PLGA/n-HA scaffolds. Vancomycin and BMP-2 were continuously and regularly eluted from the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds. The PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds promoted MC3T3-E1 cell survival and proliferation and enhanced ALP activity and calcium deposition compared with the PLGA/n-HA and PLGA/n-HA/VAN scaffolds. Additionally, the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds significantly facilitated new bone formation and inhibited bone infection in IBD rabbit models. The rabbits implanted with the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited normal heart, lung, and kidney histologies and normal serum biochemical indices, suggesting the safety of the scaffolds.Conclusion The 3D-printed PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited both antibacterial and osteoinductive activities in IBD.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 20
·15403
·
IF 5.6
Li Chen,Meng Tian,Jing Yang,Zhenxu Wu
Polymer microspheres have recently shown outstanding potential for bone tissue engineering due to their large specific surface area, good porosity, injectable property, good biocompatibility, and biodegradability. Their good load-release function and surface modifiability make them useful as a carrier of drugs or growth factors for the repair of bone defects in irregularly injured or complex microenvironments, such as skull defects. In this study, berberine (BBR)-encapsulated poly(lactic-co-glycolic acid) (PLGA)/hydroxyapatite (HA) microspheres were fabricated using electrified liquid jets and a phase-separation technique, followed by modification with the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth–factor-1 (DOPA-IGF-1). Both the BBR and the IGF-1 exhibited sustained release from the IGF-1@PLGA/HA-BBR microspheres, and the composite microspheres exhibited good biocompatibility. The results of the alkaline phosphatase (ALP) activity assays showed that the BBR and IGF-1 in the composite microspheres synergistically promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, it was confirmed that immobilized IGF-1 enhances the mRNA expression of an osteogenic-related extracellular matrix and that BBR accelerates the mRNA expression of IGF-1-mediated osteogenic differentiation and cell mineralization. Further cellular studies demonstrate that IGF-1 could further synergistically activate the IGF-1R/PI3K/AKT/mTOR pathway using BBR, thereby enhancing IGF-1-mediated osteogenesis. Rat calvarial defect repair experiments show that IGF-1@PLGA/HA-BBR microspheres can effectively promote the complete bony connection required to cover the defect site and enhance bone defect repair. These findings suggest that IGF-1@PLGA/HA-BBR composite microspheres show a great potential for bone regeneration.Keywords:polymer microspheres;berberine (BBR);IGF-1;bone regeneration;osteogenic differentiation
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Advanced Healthcare Materials
·
2019
·Vol. 8
·期 23
·1900965
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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.
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Materials Today Bio
·
2025
·
IF 10.2
Ling Wang,Jie Li,Danya Zhang,Songwei Tan,Guiying Jiang,Xueqian Wang,Fei Li,Ying Zhou,Pingbo Chen,Rui Wei,Ling Xi
Metastasis and recurrence are the main causes of failure in the treatment of ovarian cancer (OC). Immunotherapy has brought new opportunities for cancer treatment, but the presence of the immunosuppressive tumor microenvironment limits its application in OC. Here, we prepared a kind of intelligent nanomicelles that could inhibit OC metastasis and recurrence by combining photothermal tumor ablation and immune remodeling. In this study, Indocyanine green (ICG), a photosensitizer and Monophosphoryl lipid A (MPLA), a Toll-like receptor 4 agonist, were encapsulated into the core of PEG-PLGA nanocarrier, and the surface was further modified with tumor-targeting peptide TMTP1. The formed TP1-IM nanomicelles with enhanced tumor accumulation could enable robust photothermal ablation of the primary tumor, and induce immunogenic cell death, release tumor-associated antigens, and DAMPs to form an endogenous in situ tumor vaccine by a single intravenous injection, which could effectively inhibit the growth of OC. Moreover, PTT with TP1-IM nanomicelles in combination with programmed cell death ligand 1 (PD-L1) checkpoint blockade could induce strong anti-tumor immune responses, relieve the immunosuppressive tumor microenvironment, and thus effectively inhibit the metastasis of OC. In addition, the combination strategy could produce long-term immune memory effects in treated mice to prevent the recurrence of tumors. Our work provides a new and individualized strategy for the treatment of OC and is expected for clinical transformation in the future for most components are clinically approved.
研究领域:
癌症研究
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纳米医学
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免疫治疗
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生物医学工程
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JOURNAL OF NANOPARTICLE RESEARCH
·
2025
·Vol. 27
·期 10
·1-16
·
IF 2.6
Zhu Junqiao,Tang Wei,Sun Zhiting,Zhu Xinhai,Quan Qiang,Yin Jiaxin,Huang Qiugui,Jia Guoxia,Zhao Yang,Tang Yuqin,Zhang Yan,Xie Linhao,Zhao Jianfu
Multiple cycles of transarterial embolization chemotherapy for hepatocellular carcinoma (HCC) can easily cause the overexpression of P-glycoprotein (P-gp), leading to multidrug resistance (MDR) of HCC. Herein, we linked PLA (polylactic acid) with doxorubicin (DOX) through acid-sensitive hydrazone bonds to prepare PLA-ADH/DOX. Then, PLA-ADH/DOX and disulfiram (DSF) were physically encapsulated into PLGA-PEG (polylactic-co-glycolic acid-polyethylene glycol) as the backbone to fabricate a drug delivery system (DOX/DSF NPs) by nanoprecipitation and emulsion solvent evaporation method. The data of physicochemical characterization showed that DOX/DSF NPs enabled excellent stability at room temperature and pH sensitivity in an acidic environment. More importantly, DOX/DSF NPs could avoid P-gp-mediated efflux through endocytosis pathways and inhibit the function of P-gp by DSF, which increases cellular uptake of DOX in HepG2/DOX cells (hepatocellular DOX-resistant cancer cell line) and promotes DOX to enter the nucleus of HepG2/DOX cells for exerting the therapeutic effect in vitro. In addition, DOX/DSF NPs could increase intracellular reactive oxygen species (ROS) levels and reduce intracellular adenosine triphosphate (ATP) levels, thereby further inhibiting the function of P-gp, increasing intracellular concentration of drugs, and ultimately overcoming MDR in HCC. Hence, the combination of DOX and DSF delivered by DOX/DSF NPs with pH-sensitive and sequentially controlled drug release may provide a new way for MDR of HCC.
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POLYMERS FOR ADVANCED TECHNOLOGIES
·
2023
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IF 3.4
Chihao Gao,Lixia Pan,Jie Song,Min Wei,Haozhi Sun,Feng Su,Xin Shen,Suming Li
Valsartan is almost insoluble, resulting in very low bioavailability. Preparing prolonged sustained-release systems to achieve valsartan drug delivery is essential. Herein, two types of poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles loading valsartan and carboxymethyl chitosan/aldehyde sodium hyaluronate hydrogels were prepared. The nanoparticles and hydrogel composites(NPs@Gel) were obtained by physical mixing. The NPs@Gel composites have swelling ratios within the scope from 157.87% to 206.51% and mass loss within the scope from 12.85% to 17.32%, influenced by incorporating PEG-PLGA nanoparticles. Moreover, the NPs@Gel composites had properties of self-healing and injection proven by rheological measurements. Importantly, adding nanoparticles could significantly reduce the swelling ratios of the hydrogels by shrinking the void fraction and enhancing the mechanical properties. Meanwhile, NPs@Gel composites also present excellent biocompatibility as evidenced by hemolysis test and MTT assay. Therefore, a potential prolonged sustained-release system of NPs@Gel for the delivery of valsartan was achieved.
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