查找使用阿拉丁产品的科研文献

Dual-layer conduit containing VEGF-A – Transfected Schwann cells promotes peripheral nerve regeneration via angiogenesis

Yuye Huang,Kai Ye,Andong He,Shaobo Wan,Miaoben Wu,Donghao Hu,Kailei Xu,Peng Wei,Jun Yin

Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. Statement of significance Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.

Preparation and in vivo effectiveness evaluation of heparin-loaded PLGA@PCL core-shell fiber small-diameter vascular grafts

Yonghao Xiao,Han Wang,Yuhao Jiao,Yuehao Xing,Lin Ye,Ai-ying Zhang,Xue Geng,Fanshan Qiu,Zengguo Feng,Hongbo Chen,Yongquan Gu

Cardiovascular disease has become the leading cause of death. It is the common goal for researchers worldwide to develop small-diameter vascular grafts (SDVGs) which could meet clinical needs. In this study, PLGA@PCL core-shell structural fibrous SDVGs was fabricated by coaxial electrospinning process, and then the surface heparinization of the vascular material was carried out after H2N-PEG-NH2 fixed on sodium hydroxide-treated electro-spun PCL tubes. Finally, the long-term patency and tissue regeneration of the grafts were evaluated in vivo through the rabbit carotid artery replacement model. The results indicate that the heparin-modified PLGA@PCL core-shell structural fibrous SDVGs achieved long-term patency and the arrangement of collagen and elastin in the neointima was similar to the native vessel in the rabbits after 9 months. After 3 months postoperatively, endothelialization was almost complete, and vascular calcification was also observed. It can be concluded that surface heparinization is a feasible modification method for in situ tissue-engineered vascular grafts, and controlling the occurrence of vascular calcification is another important issue to be solved in the development of SDVGs, and it is also the focus of our next research work.

Microfluidic Engineering of Core–Shell PLGA Microspheres with Adjustable Shell Thickness for Long-Acting Delivery of Leuprolide Acetate

Jiaze Dou,Ruoxin Wei,Xingwei Jin,Lian Cen

Small hydrophilic peptide drugs usually require long-acting microsphere-based delivery systems to maintain therapeutic efficiency. The main challenge is the identification of a technology and specific process parameters that are capable of precisely regulating the key property, which can tune the drug encapsulation and release behaviors of microspheres. A three-phase glass capillary microfluidic device was thus proposed to fabricate core–shell PLGA microspheres encapsulated with leuprolide acetate (LA) as a representative hydrophilic peptide, and the shell thickness of microspheres was tuned by controlling the flow rate ratios to explore its effect on LA loading and release. The Qm/Qi ratio was adjusted from 1 to 6 to yield PLGA microspheres of different core–shell structures. HPLC was employed to determine the LA concentration within microspheres and evaluate their long-term release behavior. It was shown that uniform microspheres of 80 μm with distinct core–shell structure were formed using this device, and shell thickness was successfully regulated via the control of the flow rate ratios. The increases in shell thickness significantly enhanced the encapsulation efficiency (EE) (from 65.48% to 87.66%), reduced the initial burst release (from 59.24% to 23.52%), and prolonged the sustained-release duration from approximately 30 to 70 days. Under the appropriate thickness, the LA concentration could also function to improve the encapsulation properties. Overall, this work provides mechanistic insight into the structure–performance relationship of microfluidic manipulated core–shell PLGA microspheres for long-term release of LA and establishes a rational foundation for the design of predictable long-acting peptide delivery systems.

Development of thymol-loaded biocompatible PLA/PLGA composite nanoparticles for oral health care application: Antimicrobial and antibiofilm activities

Linxuan Jin,Wei Li,Yunlong Han,Li Zhang,Xinke Yan,Yue Zhang

Thymol-loaded PLA, PLGA, and PLA-PLGA nanoparticles were fabricated for oral care applications. • Nanoparticles achieved sustained thymol release with enhanced antimicrobial and antibiofilm activity. • Nanoparticle encapsulation enhanced thymol-induced microbial membrane damage. • The PLA-PLGA formulation balanced high cytocompatibility and low hemolysis without compromising antimicrobial efficacy. Biocompatible nanoformulations offer a promising approach to enhancing the bioavailability and bioactivity of phytochemicals such as thymol, thereby expanding their potential for oral healthcare applications. This study fabricated thymol-loaded polylactic acid (PLA), poly (lactic- co -glycolic acid) (PLGA), and PLA-PLGA blend nanoparticles through single-emulsion solvent evaporation, and compared their physicochemical properties, antimicrobial activity, and preliminary biological safety comprehensively. All nanoparticles exhibited a spherical and uniform morphology, while increasing the PLGA content resulted in a slightly more porous surface structure. Thymol release from all formulations followed a biphasic release profile, with PLGA nanoparticles showing the highest encapsulation efficiency and the fastest release. In contrast, PLA-PLGA blend nanoparticles provided more sustained thymol release, leading to prolonged antimicrobial and antibiofilm activities against the oral wound-associated pathogens Escherichia coli and Staphylococcus aureus , as well as the major oral microorganisms Streptococcus mutans and Candida albicans . Fluorescence staining and SEM observations demonstrated that nanoparticle encapsulation enhanced thymol-induced membrane permeabilization and structural damage to microbial cells. At an equivalent thymol concentration, PLA-PLGA blend nanoparticles maintained approximately 95% cell viability and caused less than 5% hemolysis without compromising antimicrobial efficacy, supporting their further development for local oral infection control. Download: Download high-res image (275KB) Download: Download full-size image

CGRP-releasing PLGA/nHA/GO composite microspheres enhance distraction osteogenesis via activation of the cAMP/PKA/CREB pathway

Yimurang Hamiti,Kai Liu,Xin Yang,Sulong Wang,Xiriaili Kadier,Aihemaitijiang Yusufu

Large bone defects present significant clinical challenges, with distraction osteogenesis (DO) requiring prolonged treatment periods and yielding suboptimal outcomes. Calcitonin gene-related peptide (CGRP) demonstrates potent bone-forming activity but suffers from rapid degradation and a short half-life, limiting its therapeutic applications. This study engineered sustained-release CGRP microspheres using poly(D,L-lactide-co-glycolide)/nano-hydroxyapatite/graphene oxide (PLGA/nHA/GO) composite matrices via W/O/W double emulsion-solvent evaporation method to address these limitations. The fabricated microspheres exhibited uniform spherical morphology (51.15 ± 0.40 μm), high encapsulation efficiency (86.14 ± 2.5 %), and sustained CGRP release over 42 days. In vitro studies compared four groups: control (untreated), blank microspheres, free CGRP solution, and CGRP-loaded microspheres. CGRP microspheres significantly enhanced rat bone marrow mesenchymal stem cell proliferation, migration capacity, and osteogenic differentiation compared to all other treatment groups. Mechanistic investigations confirmed activation of the cAMP/PKA/CREB signaling pathway with upregulation of osteogenic transcription factors (Runx2, Osterix) and bone matrix proteins (osteopontin, osteocalcin). In a rat femoral distraction osteogenesis model, CGRP microspheres demonstrated superior bone regeneration compared to control, blank microspheres, and free CGRP groups: substantially increased bone mineral density, significantly improved biomechanical properties, and accelerated bone formation. Histological analysis confirmed enhanced bone maturation and integration This engineered sustained-release system represents a promising therapeutic platform for enhancing bone regeneration through targeted molecular pathway activation, offering significant potential for clinical translation in orthopedic applications.

Adhesive polyelectrolyte coating through UV-triggered polymerization on PLGA particles for enhanced drug delivery to inflammatory intestinal mucosa

Zhang Jie,Yin Yi-jing,Wang Xing-wang,Lu Wei-qi,Chen Zhao-yang,Yu Chao-hui,Ren Ke-feng,Xu Cheng-fu

Administering medication precisely to the inflamed intestinal sites to treat ulcerative colitis (UC), with minimized side effects, is of urgent need. In UC, the inflammation damaged mucosa contains a large number of amino groups which are positively charged, providing new opportunities for drug delivery system design. Here, we report an oral drug delivery system utilizing the tacrolimus-loaded poly (lactic-co-glycolic acid) (TAC/PLGA) particles with an adhesion coating by in situ UV-triggered polymerization of polyacrylic acid and N-hydroxysuccinimide (PAA-NHS). The negatively charged carboxyl groups effectively interact with the positively charged focal mucosa, and the NHS ester groups form the covalent bonds with the amino groups, thereby synergically enhancing the adhesion of the PLGA particles to the focal mucosa. Our findings reveal that, compared to the naked particles, the PAA-NHS coating increases the adhesion of particles to the inflammatory intestine. In a dextran sulfate sodium-induced acute colitis mouse model, the TAC/PLGA particles with PAA-NHS coating exhibits substantial retention of TAC within the inflammatory intestine, enhancing drug delivery efficiency and therapeutic effects. This approach holds promise for UC management, minimizing systemic side effects and optimizing therapeutic outcomes. Graphical abstract

Mechanical strength affecting the penetration in microneedles and PLGA nanoparticle-assisted drug delivery: Importance of preparation and formulation

Geng Lu,Baohua Li,Luping Lin,Xiaofang Li,Junfeng Ban

Microneedles (MNs) prepared from polymeric materials are painless and minimally invasive, safe and efficient, but they hindered by low mechanical strength and single diverse drug release pattern. Due to the distinctive mechanical strength and dimensions of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), the integration of nano-technology with microneedles can effectively improve penetration and delivery efficiency through the stratum corneum. We herein designed a simple paroxetine (PAX)-loaded PLGA nanoparticles-integrated dissolving microneedles system (PAX-NPs-DMNs), aiming to improve the bioavailability of PAX through the synergistic permeation-enhancing effect of dissolving microneedles (DMNs) and NPs. PAX-NPs-DMNs had a complete tips molding rate ( N eff ) of (94.06 ± 2.16) %, a 15×15 quadrangular-conical microneedle array and an overall fracture force of 301.10 N, which were improved nearly 0.50 times compared with the blank microneedles (HA-DMNs) and PAX microneedles (PAX-DMNs). PAX-NPs-DMNs could extend the release duration of PAX from 1 h to 24 h and the cumulative permeability per unit area (Q n ) was 47.66 times and 7.37 times higher than the PAX and the PAX-DMNs groups. PAX-NPs-DMNs could be rapidly dissolved within 10 min without hindering skin healing or causing adverse reactions. This study confirmed that PAX-NPs-DMNs can effectively improve the bioavailability of PAX and the mechanical strength of DMNs, which can easily penetrate the skin to provide sustained and painless delivery without causing adverse effects, thus offering a more convenient and effective method for central nervous diseases.

Multifunctional tumor-targeted PLGA nanoparticles delivering Pt(IV)/siBIRC5 for US/MRI imaging and overcoming ovarian cancer resistance

Yanhua Zhang,Yang Dong,Hao Fu,Hui Huang,Zhihua Wu,Meng Zhao,Xupeng Yang,Qianqian Guo,Yourong Duan,Ying Sun

Cisplatin (Pt(II)) resistance is an important factor in the high mortality rates of ovarian cancer. Herein, we synthesized multifunctional tumor-targeted poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs-cRGD) for monitoring therapeutic effects by dual-mode imaging and overcoming cisplatin resistance. Uniformly sized NPs-cRGD demonstrated controlled and sustained release of drugs and genes, excellent gene loading and gene protection capacity, good storage stability and no serum-induced aggregation in vitro . NPs-cRGD demonstrated clear, targeting and prolonged ultrasound imaging and magnetic resonance imaging (MRI) in vivo . The targeting of NPs-cRGD combined with ultrasound facilitated nanoparticle penetrattion into cells; entry was time-dependent. NPs-cRGD escaped from lysosomes , thereby preventing siBIRC5 degradation, which enabled siBIRC5 to efficiently inhibit the antiapoptosis effects of BIRC5 in SKO3-DDP to overcome the antiapoptosis properties of resistant cells. Furthermore, Pt(IV) in NPs-cRGD exhausted glutathione (GSH), thereby increasing drug accumulation to effectively increase Pt(II) levels. The subsequent combination of Pt(II) with DNA prevented the expressions of genes and upregulated the expression of p53 to induce the mitochondria apoptosis pathway. The reduced GSH activity and the generation of Pt(II) further promoted high levels of reactive oxygen species (ROS) to induce cell apoptosis. Therefore, NPs-cRGD with ultrasound promoted the apoptosis of resistant ovarian cancer cells by multiple mechanisms, including increased cellular drug accumulation, reversed antiapoptotic effects by siBIRC5, and enhanced ROS levels. In a tumor-bearing nude mice model, NPs-cRGD with US demonstrated excellent tumor-targeting, high efficiency tumor inhibition and low systemic toxicity. Therefore, NPs-cRGD provides a means to monitor treatment processes and can be combined with ultrasound treatment to overcome ovarian cancer resistance in vitro and in vivo .

Uptake and trafficking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model

Zibei Lin,Long Xi,Shaokui Chen,Jinsong Tao,Yan Wang,Xin Chen,Ping Li,Zhenping Wang,Ying Zheng

Psoriasis is an autoimmune inflammatory disease, where dendritic cells (DCs) play an important role in its pathogenesis. In our previous work, we have demonstrated that topical delivery of curcumin-loaded poly (lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) could treat Imiquimod (IMQ)-induced psoriasis-like mice. The objective of this study is to further elucidate biofate of PLGA NPs after intradermal delivery including DCs uptake, and their further trafficking in psoriasis-like mice model by using fluorescence probes. Two-sized DiO/DiI-loaded PLGA NPs of 50 ± 4.9 nm (S-NPs) and 226 ± 7.8 nm (L-NPs) were fabricated, respectively. In vitro cellular uptake results showed that NPs could be internalized into DCs with intact form, and DCs preferred to uptake larger NPs. Consistently, in vivo study showed that L-NPs were more captured by DCs and NPs were firstly transported to skin-draining lymph nodes (SDLN), then to spleens after 8 h injection, whereas more S-NPs were transported into SDLN and spleens. Moreover, FRET imaging showed more structurally intact L-NPs distributed in skins and lymph nodes. In conclusion, particle size can affect the uptake and trafficking of NPs by DCs in skin and lymphoid system, which needs to be considered in NPs tailing to treat inflammatory skin disease like psoriasis.

Preparation of PLGA microspheres loaded with 10-hydroxycamptothecin and arsenic trioxide and their treatment for rabbit hepatocellular carcinoma.

Wu Y,Du D,Chen J,Liu C

Objective This study aims to study the preparation method of arsenic trioxide (As 2 O 3 ) polylactic-co-glyconlic acid (PLGA) microspheres and 10-hydroxycamptothecin (HCPT) PLGA microspheres and explore their therapeutic effects as embolic agents for VX2 hepatocellular carcinoma in rabbits. Methods As 2 O 3 and HCPT PLGA microspheres were prepared by multiple emulsion solvent evaporation method. Scanning electron microscopy (SEM) and particle size distribution were used to analyze the morphology, the drug sustained release ability was observed by the release of microspheres in vitro. The rabbit model of VX2 hepatocellular carcinoma was established and the hepatocellular carcinoma was treated with combined microspheres. The therapeutic effects were detected by qPCR, western blotting, HE staining and immunohistochemical methods. Results The PLGA microspheres loaded with As 2 O 3 and HCPT were successfully prepared by optimizing the ratio. The particle size was between 30 and 50 μm. In vitro release results showed that PLGA microspheres loaded with As 2 O 3 released completely in 10 days and PLGA microspheres loaded with HCPT released completely in 12 days. Western blotting and qPCR results showed that the expression of ALDH1A1 and Nanog decreased significantly in treatment group. HE staining and immunohistochemical analysis showed that the expression of CD31, HIF and VEGF decreased significantly and the apoptosis of tissues was obvious. Conclusion The combination of As 2 O 3 and HCPT PLGA microspheres as embolization for VX2 hepatocellular carcinoma in rabbits has significant therapeutic effect.

Enhanced cellular uptake of folic acid–conjugated PLGA–PEG nanoparticles loaded with vincristine sulfate in human breast cancer

Jianian Chen,Shaoshun Li,Qi Shen,Huijuan He,Yi Zhang

The aim of this paper is to evaluate the cellular uptake of vincristine sulfate-loaded poly(lactic-co-glycolic acid)–polyethylene glycol (PLGA–PEG) nanoparticles with the folic acid modification (PLGA–PEG–folate NPs). PLGA–PEG–folate NPs were prepared using a water–oil–water emulsion solvent evaporation method. The particle size, surface morphology, drug encapsulation efficiency, and the drug release behavior were investigated. The NPs exhibited a biphasic drug release with a moderate initial burst followed by a sustained release profile. Internalization of the NPs labeled with coumarin- 6 by MCF-7 (Michigan Cancer Foundation-7) human breast cancer cells was quantitatively measured by microplate reader, and qualitatively analyzed by fluorescent microscopy and confocal laser scanning microscopy. The results showed PLGA–PEG–folate NPs achieved significantly higher cellular uptake in the folic acid receptor overexpressed MCF-7 cells, compared to PLGA–mPEG NPs without the folic acid modification. Due to the enhanced cellular uptake, PLGA–PEG–folate NPs displayed the highest cytotoxicity. Judged by IC50 after 24 h culture, the therapeutic effects of the drug formulated in the NPs with surface modification could be 1.52 times, 3.91 times higher than that of PLGA–mPEG NPs and free vincristine sulfate, respectively.

Study on preparation, characterization and multidrug resistance reversal of red blood cell membrane-camouflaged tetrandrine-loaded PLGA nanoparticles

Xiao Que,Jing Su,Pengcheng Guo,Zul Kamal,Enge Xu,Siyu Liu,Jieyu Chen,Mingfeng Qiu