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Artificial Cells Nanomedicine and Biotechnology · 2018 · IF 3.026

Collagen-based porous scaffolds containing PLGA microspheres for controlled kartogenin release in cartilage tissue engineering

Xiaomin Sun,Jianhua Wang,Yingying Wang,Qiqing Zhang

A scaffold composed of different collagen (COL)/chitosan (CS)/hyaluronic acid sodium (HAS) salt ratios was evaluated by determining porosity, swelling, loss rate in hot water, mechanical property, and cell proliferation to obtain optimum conditions for manufacturing porous scaffolds. Results showed that the optimal ratio of COL/CS/HAS salt porous scaffold was 1:1:0.1. High swelling and loss rate of scaffolds/microspheres (MPs) could lead to high diffusion rate of MPs from the scaffolds, causing an increase in the kartogenin (KGN) release. The porous scaffolds at optimum conditions had a maximum amount of KGN release. Results of in vitro fluorescence staining and cell proliferation suggested that scaffolds/MPs had good biocompatibility and the capability to promote bone marrow stromal cell proliferation, cartilage tissue regeneration, and integration between the repaired and surrounding cartilages. Therefore, this composite could be a promising material for cartilage repair and regeneration, which could be effective in the knee osteoarthritis treatment.

CAS / MDL: 26780-50-7
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2023 ·Vol. 33 ·期 18 ·2214126 · IF 19

Multifunctional BPs/MT@PLGA-ALE Nanospheres for Treatment of Osteoporotic Fracture with Near-Infrared Irradiation

Kai Zheng,Jiaxiang Bai,Wanling Chen,Yaozeng Xu,Huilin Yang,Wei Li,Penghui Li,Liping Tong,Huaiyu Wang,Paul K. Chu,Dechun Geng

Osteoporotic fracture, which is a clinical complication of osteoporosis featured with the imbalance of bone homeostasis. Non-surgical intervention is frequently required post-operatively to ameliorate the fracture healing. Nevertheless, current non-surgical therapies are mostly performed in a non-targeted manner without giving enough consideration to the pathological characteristics of osteoporosis. Therefore, it is highly desirable to develop an optimal strategy for promoting fracture healing under osteoporotic conditions. In this study, a multifunctional therapeutic nanoplatform is designed to work in conjunction with near-infrared irradiation. Specifically, poly (lactic-co-glycolic acid) (PLGA) is functionalized with alendronate (ALE) and black phosphorus nanosheets (BPs) together with melatonin (MT) molecules are encapsulated by PLGA-ALE to produce the multifunctional BPs/MT@PLGA-ALE nanospheres. In this structure, BPs degrade gradually and deliver mild photothermal effects to facilitate bone regeneration, whereas MT has the dual-capability of suppressing osteoclastogenesis and promoting osteogenesis. Moreover, ALE endows the nanoplatform with the reliable bone-targeting capacity to improve the therapeutic effects. The combination of BPs/MT@PLGA-ALE nanospheres and photothermal therapy significantly improve post-surgical healing of osteoporotic fracture by modulating the tumor necrosis factor and cell death-related signaling pathways. This study reveals a promising strategy to treat osteoporotic fracture and broadens the application of nanomaterials in the biomedical field.

研究领域: 生物医学工程 · 纳米技术 · 骨科 · 药学
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Drug Delivery and Translational Research · 2023 · IF 5.4

Construction of PLGA nanoparticles modified with RWrNM and DLPC and their application in acute rhinosinusitis

Tao Wanjun,Xie Pei,Huang Chengyuan,Wang Ying,Huang Yu,Yin Zongning

In an effort to overcome the nasal mucus barrier and epithelial barrier, as well as reduce entry into the bloodstream, we designed RWrNM and DLPC-modified PLGA nanoparticles (PDR-NPs). These nanoparticles were further encapsulated with dexamethasone acetate (Dexac) to form Dexac/PDR-NPs. Transmission electron microscopy (TEM) analysis revealed their spherical shape with an outer lipid layer. Dynamic light scattering (DLS) determined their particle size to be 125.77 ± 2.01 nm, with a polydispersity index (PDI) of 0.139 ± 0.029. The experimental results demonstrate that DLPC-modified PLGA nanoparticles can effectively reduce interactions with mucin at different concentrations, decrease aggregation, and facilitate their crossing of the mucus barrier. Additionally, results from the cellular uptake assay revealed a significantly greater uptake of PDR-NPs by inflammatory RAW 264.7 cells (2.99-fold higher than that of free C6, p  < 0.0001) and inflammatory HUVECs (7.20-fold higher than that of free C6, p  < 0.0001). Furthermore, Dexac/PDR-NPs effectively reduced the levels of inflammatory factors nitric oxide (NO) ( p  < 0.001) and interleukin-6 (IL-6) ( p  < 0.05) in the supernatant of inflammatory RAW 264.7 cells. Intravital imaging of rats revealed that PDR-NPs had a longer residence time in inflamed nasal tissue compared to PD-NPs. Furthermore, in vivo pharmacodynamic experiments showed that Dexac/PDR-NPs effectively reduced the symptoms of nasal inflammation, lowered the pH of nasal secretions, decreased serum inflammatory factor levels (TNF-α and IL-6), and reduced nasal mucosal inflammatory factor levels (IL-1β), while also reducing the degree of inflammation in the nasal mucosa. Both cytotoxicity assays and in vivo results indicate that PDR-NPs have a good safety profile. PDR-NPs not only overcome the nasal mucus barrier but also reduce the systemic toxicities associated with drug entry into the circulation by enhancing the targeting of inflammatory macrophages and inflammatory vascular endothelial cells. PDR-NPs allow for an “open sources and cut costs” treatment strategy to increase drug retention in the inflamed nasal tissues, reducing toxicity and increasing efficacy. In conclusion, PDR-NPs can be a promising drug delivery system for the local treatment of acute rhinosinusitis. Graphical Abstract

✓ 已验证 产品关联 DOI PubMed 高影响因子
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BME Frontiers · 2024 · IF 5

Controllable Thrombolysis Using a Nanobubble-Imaging-Guided rtPA Targeted Delivery Strategy

Jian Tang,Huiting Xu,Mingxi Li,Yang Liu,Fang Yang

Objective: The objective of this work is to design and fabricate a novel multifunctional nanocarrier combining thrombus-targeted imaging and ultrasound-mediated drug delivery for the theranostics of thrombotic diseases. Impact Statement: This study develops a new technology that can accurately visualize the thrombus and deliver drugs with controllable properties to diagnose and treat thrombotic diseases. Introduction: Thrombotic diseases are a serious threat to human life and health. The diagnosis and treatment of thrombotic diseases have always been a challenge. In recent years, nanomedicine has brought new ideas and new methods for the theranostics of thrombotic diseases. However, there are also many problems need to be solved, such as biosafety and stability of nanocarriers, early diagnosis, and timely treatment of thrombotic diseases, difficulty in clinical translation. Methods: The S1P@CD-PLGA-rtPA nanobubbles (NBs) were prepared by integrating sulfur hexafluoride (SF6)-loaded poly (D, L-lactide-co-glycolide) (PLGA) NBs, cyclodextrin (CD), sphingosine-1-phosphate (S1P), and recombinant tissue plasminogen activator (rtPA). Results: S1P@CD-PLGA-rtPA NBs had rapid and excellent thrombosis targeting imaging performance based on the specific interaction of S1P–S1PR1 (sphingosine-1-phosphate receptor 1). Furthermore, S1P@CD-PLGA-rtPA NBs that specifically targeting to the thrombosis regions could also respond to external ultrasound to achieve accurate and efficient delivery of rtPA to enhance the thrombolysis effectiveness and efficiency. Conclusion: This study proposes a new idea and strategy of targeting thrombus in rats via the specific interaction of S1P–S1PR1. On this basis, the acoustic response properties of bubble carriers could be fully utilized by combining thrombus-specific targeted imaging and ultrasound-mediated drug delivery for effective thrombolysis, which is expected to be applied in targeted diagnosis and treatment of thrombotic diseases in the future.

CAS / MDL: 25952-53-8 106627-54-7
研究领域: 纳米医学 · 治疗诊断学 · 生物医学工程 · 药学 · 医学成像
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MATERIALS & DESIGN · 2024 · IF 7.6

Electrospunned nanofiber membranes of PTH-related peptide loaded biopolymers for osteoporotic bone defect repair

Renxin Chen,Junwu Wang,Lei Chen,Zouwei Li,Qinyu Feng,Fangqi Chen,Zhuowen Hao,Tianhong Chen,Guang Shi,Qi Zhang,Yi Wang,Tao Ding,Jingfeng Li

Despite the rapid development of the application of tissue engineering techniques in regenerative bone repair, the repair of severe pathologic bone defects, represented by osteoporotic bone defects, is still a huge challenge. Recent studies have identified local delivery of parathyroid hormone relative peptides (PTHrPs) as a novel pathway for bone repair as well, but how to load and locally release PTHrPs for good bone repair is a major obstacle. Here, a biopolymer of PLGA-PLL loaded with PTHrP1 is electrospunned into nanofiber membranes for guided bone regeneration. In vitro experiments show that PLGA-PLL synergized with PTHrP1 significantly promote osteogenic differentiation and angiogenesis, providing a favorable bone regeneration microenvironment. In vivo experiments show that the membrane recruits endogenous stem cells and promotes their ectopic osteogenic differentiation in an osteoporotic environment. Furthermore, the membrane can promote osteogenic differentiation and angiogenesis in situ and improve the local osteoporotic microenvironment, ultimately promoting the repair of bone defects. Therefore, present study provides a promising strategy for local delivery of PTH, which opens a new pathway for the treatment of osteoporotic bone defects.

CAS / MDL: 123-03-5 75-89-8
研究领域: 组织工程 · 再生医学 · 生物材料 · 骨修复
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International Journal of Nanomedicine · 2023 · IF 8

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system

Liting Guo,Haijun Zhang,Fei Wang,Ping Liu,Yonglu Wang,Guohua Xia,Ran Liu,Xueming Li,Haixiang Yin,Hulin Jiang,Baoan Chen

The study investigated the reversal of multidrug resistance (MDR) and the biodistribution of nanoparticles (NPs) that target leukemia cells in a nude mice model via a surface-bound transferrin (Tf). The cytotoxic cargo of daunorubicin (DNR) and tetrandrine (Tet) was protected in the NPs by an outer coat composed of polyethylene glycol (PEG)-poly-l-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) NPs. Injection of DNR-Tet-Tf-PEG-PLL-PLGA NPs into nude mice bearing MDR leukemia cell K562/A02 xenografts was shown to inhibit tumor growth, and contemporaneous immunohistochemical analysis of tumor tissue showed the targeted NPs induced apoptosis in tumor cells. Targeted tumor cells exhibited a marked increase in Tf receptor expression, with noticeable decreases in P-glycoprotein, MDR protein, and nuclear factor κB, as assessed by quantitative real-time polymerase chain reaction and Western blot analysis. Moreover, the concentration of DNR was shown to increase in plasma, tumor tissue, and major organs. Flow cytometry analysis with a near-infrared fluorescent (NIRF) dye, NIR797, was used to study the effectiveness of Tf as a targeting group for leukemia cells, a finding that was supported by NIRF imaging in tumor-bearing nude mice. In summary, our studies show that DNR-Tet-Tf-PEG-PLL-PLGA NPs provide a specific and effective means to target cytotoxic drugs to MDR tumor cells.

研究领域: 药学 · 肿瘤学 · 纳米技术 · 分子生物学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2026 · IF 6

Modulating meloxicam existing forms in PLGA microspheres to achieve drug sustained release and efficient osteoarthritis treatment

Haonan Wu,Fan Wang,Yameng Qu,Fujia Yang,Liandong Hu

Poly (lactic-co-glycolic acid) (PLGA) microspheres are widely used for controlled drug delivery, but the drug existing state in the microspheres significantly influences the characteristics of microspheres. The focus of the present study was to formulate meloxicam injectable sustained release microspheres (MLX-MS) and to investigate the influence of the drug existing state within the microspheres on the release properties, degradation and to evaluate the intra-articular (IA) treatment efficacy of osteoarthritis (OA). Different MLX-MS were prepared by changing drug existing forms (microcrystal, particle and molecular state) by the method of cosolvent combination or micronized drug and they were characterized by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD) and in vitro release. The therapeutic effect of MLX-MS was investigated using OA rabbits after IA injection. The degradation, drug retention, and pharmacodynamics were also assessed. The results highlighted that the release and degradation of MLX-MS in the joint cavity were directly correlated to the drug existing state. This study offers crucial insights for developing sustained-release injectable MLX-MS, the microspheres with drug existing in molecular state (Mol-MS) were the optimum formulation which can provide sustained release and more effective therapy of joint inflammation.

CAS / MDL: 9002-89-5
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ACS Applied Bio Materials · 2026 · IF 5.6

Evaluation of Remodeling and Regeneration of Electrospun PLGA@PCL/Elastin Small-Diameter Vascular Grafts In Vivo

Yonghao Xiao,Yuanguo Zhang,Yuehao Xing,Ming Gao,Yuting Ge,Hailei Li,Xin Wu,Lin Ye,Zeng-guo Feng

Bypass vascular grafting is an effective treatment for cardiovascular disease. Currently, small-diameter vascular grafts (SDVGs, inner diameter <6 mm) for peripheral revascularization, especially for lower limb revascularization, are in high demand. Previously, we prepared and investigated PLGA@PCL SDVGs with core/shell fibers. In this study, PLGA@PCL/elastin core/shell fibers (PCEs) SDVGs were further prepared by electrospinning, so as to enhance the vascular regeneration performance through the introduction of exogenous soluble elastin. The cross-linking effects of elastin with different cross-linking reagents on PCEs SDVGs were subsequently explored. Among them, PCEs SDVGs cross-linked with 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDCI) and N-hydroxysuccinimide (NHS) retained the most soluble elastin content and achieved a compliance of 1.74 ± 0.62%/mmHg × 10–2, a bursting pressure of 1750 mmHg, and a tensile strength of 2.09 ± 0.51 MPa, which are mostly close to those of human saphenous vein. Subsequently, in vivo transplantation in the abdominal aorta showed that all implanted SDVGs cross-linked by EDC/NHS (PCEsEN) remained patent without aneurysm formation. Histological staining results further showed that the introduction of elastin not only promoted the degradation of SDVGs but also accelerated the formation of neointimal tissue and suppressed the calcification. Thus, PCEsEN shows promising potential to be translated into SDVGs in clinic.

CAS / MDL: 4432-31-9
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 · IF 12.6

Astaxanthin and Dihydroartemisinin loaded PLGA NPs for atherosclerosis therapy via regulating lipid metabolism and immune microenvironment

Hu Jiayao,Liu Hao,Wu Yizhou,Dong Xiaoyan,Tang Dongying,Yan Wei,Liu Bin,Zhou Hongyan

The active ingredients of Traditional Chinese Medicine with diverse structures exhibited anti-inflammatory and lipid lowering functions, demonstrating significant therapeutic effects in inflammatory diseases of atherosclerosis. We incorporate Astaxanthin (AST) and Dihydroartemisinin (DHA) into PLGA NPs to synthesized HA@PLGA@AST/DHA NPs (HPAD NPs) for alleviating atherosclerosis. In vitro assay indicated that the designed HPAD NPs promoted cholesterol efflux of macrophages by enhancing selective lipophagy, which is benefit to lipid antigen degradation. Meanwhile, HPAD NPs regulated T-cell differentiation and crucially induced macrophages from pro-inflammatory M1 type to anti-inflammatory M2 type. In vivo study demonstrated that HPAD NPs decreased the necrotic core dimension and improved plaque stability in ApoE -/- mice with atherosclerosis. Overall, this research indicated the promise of HPAD NPs for the targeted therapy of atherosclerosis. Graphical abstract Schematic illustration of HPAD NPs preparation and therapeutic strategy for AS. (A) Preparation of HPAD NPs. (B) HPAD NPs reduce inflammation and prevent AS by restoring lipophagy of macrophages and promote the polarization from M1 type to M2 type to modulate the AIM.

CAS / MDL: 472-61-7
研究领域: 药剂学 · 纳米医学 · 心血管病学 · 免疫学 · 分子生物学 · 代谢生物学
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Biomaterials Science · 2025 · IF 5.7

Osteoinductive IL-8/tDM/PLGA scaffolds based on autologous BMSC recruitment and endogenous growth factor regulation

Zihao Zhao,Mengjie Xu,Zhou Zhang,Xing Yin,Ximing Pu,Juan Wang,Xiaoming Liao,Zhongbing Huang,Shunze Cao,Guangfu Yin

The in vitro expanded seed cells and the supraphysiological doses of exogenous growth factors both pose huge safety risks in bone regeneration. In this study, a novel IL-8/tDM/PLGA composite scaffold was developed, where chemokine interleukin-8 (IL-8) and transferable decellularized matrix (tDM) were uniformly overlaid on exterior and interior surfaces of poly(lactic-co-glycolic acid) (PLGA) porous substrates. The in vitro experiments confirmed that the synergy of tDM and IL-8 achieved the obvious promotion of osteogenesis and angiogenesis via enhancing chemotaxis, adhesion, spreading, osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells (BMSCs). IL-8 mediated the in situ recruitment of BMSCs and macrophages via binding with C–X–C motif chemokine receptor 2 (CXCR2), while maintaining cellular viability without inducing macrophage polarization. Moreover, tDM improved BMSC adhesion and spreading via the recognition and binding of the affinitive ligand existing in tDM by the cell adhesion molecules (CAMs) on the BMSC cytomembrane. Furthermore, tDM promoted the osteogenic differentiation and mineralization of BMSCs, benefiting from the retained growth factors. In a rat femoral defect model, the IL-8/tDM/PLGA scaffold significantly accelerated new bone mineralization and maturation through synergistic regulations of cell recruitment, matrix adhesion, and osteogenic signaling pathways. After 8 weeks post-implantation of the IL-8/tDM/PLGA scaffolds, the bone volume fraction of the newly formed bone, trabecular number, and trabecular separation at the defect site were 47%, 1.21 mm−2, and 0.50 mm, respectively, which presented significantly better bone repair effects than those in other groups. These results demonstrated that the innovative bone regeneration strategy combining chemokine-driven recruitment and endogenous tDM regulation offered a potential solution for clinical repair of large-sized bone defects.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Engineering Long-Acting apixaban loaded PLGA microspheres for the treatment of stroke caused by atrial fibrillation

Xue-Ai Liu,Yaseen Hussain,Jiawen Wang,Ping Xia,Xiang-Xiang Huang,Ming-Wei Huo,Ling-Zhi Shi,Jing-Hao Cui,Beom-Jin Lee,Renyu Huang,Yujin Ji,Minggang Wei,Qing-Ri Cao

Atrial fibrillation needs effective anticoagulation strategies because it significantly increases the risk of stroke and is the leading cause of death in adults. Apixaban – a direct FXa inhibitor poses challenges in the form of poor patient compliance and dosing errors when administered via tablets, thus necessitates a novel delivery system. Conventionally, PLGA 50/50 results in immediate release profile compared to PLGA 75/25. We hypothesized the strong hydrogen bonding between apixaban and PLGA 50/50 through simulation and proved the transformation from immediate release to long-acting release of PLGA 50/50. The present study investigated the long-acting microsphere formulation of Apixaban for stroke prevention, using a microfluidic technology-integrated S/O/W double emulsion-solvent evaporation method. The fabricated formulations in terms of Apixaban-Ms (low, medium, and high) were optimized through the single factor investigation and orthogonal experimental design, and then produced on a large scale that exhibited round and smooth surface morphology. The molecular simulations indicated sustained release mechanisms for the proposed microsphere system, which was investigated for the first time, while DSC/XRD results confirmed the drug loading into microspheres in crystal form with modified thermal properties. Furthermore, the safety and biocompatibility study of the proposed microspheres was conducted using HUVEC cell line and was found safe and biocompatible. Notably, from a pharmacological perspective the pharmacokinetic studies in the in vivo model showed prolong release profile, while both in vitro and in vivo pharmacodynamic studies of fabricated formulation showed long-lasting anticoagulant activity through FXa level reduction and enhanced APTT and PT levels. These findings in a nutshell, suggest into valuable insights of Apixaban-loaded long-acting microspheres for the clinical application in stroke prevention among patients suffering from atrial fibrillation.

CAS / MDL: 75-05-8
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2012 · IF 1.691

Preparation and characterization of electrospun PLGA/gelatin nanofibers as a drug delivery system by emulsion electrospinning

Jun Hu,Junchao Wei,Wanyun Liu,Yiwang Chen

Novel biocompatible poly(lactide-co-glycolide) (PLGA) nanofiber mats with favorable biocompatibility and good mechanical strength were prepared, which could serve as an innovative type of tissue engineering scaffold or an ideal controllable drug delivery system. Both hydrophobic and hydrophilic drugs, Cefradine and 5-fluorouracil were successfully loaded into PLGA nanofiber mats by emulsion electrospinning. The natural bioactive protein gelatin (GE) was incorporated into the nanofiber mats to improve the surface properties of the materials for cell adhesion. Nanofibrous scaffolds were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, contact angle and tensile measurements. Emulsion electrospun fibers with GE had perfect hydrophilic and good mechanical property. The in vitro release test showed thedrugs released from emulsion electrospun fibers, which achieved lower burst release. The cells cytotoxicity experiment indicated that emulsion electrospun fibers were less toxic and tended to promote fibroblasts cells attachment and proliferation, which implied that the electrospun fibers had promising potential application in tissue engineering or drug delivery.

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