EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2013
·
IF 2.987
Xiao Zhang,Gang Chen,Lu Wen,Fan Yang,A-li Shao,Xia Li,Wei Long,Lei Mu
The aim of this study was to develop novel multiple agents loaded poly ( d , l -lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) and evaluate their potential for brain delivery via inner ear administration. PLGA NPs loaded with salvianolic acid B (Sal B), tanshinone IIA (TS IIA) and panax notoginsenoside (PNS) were prepared by double emulsion/solvent evaporation method. It was observed that optimized NPs displayed satisfactory encapsulation efficiency and desired sustained-release characteristics. NPs following intratympanic administration (IT) in guinea pigs greatly improved drug distribution within the inner ear, cerebrospinal fluid (CSF) and brain tissues compared with intravenous administration (IV). Pharmacodynamic studies demonstrated that NPs following IT markedly inhibited oxidizing reactions and protected the brain from cerebral ischemia reperfusion (I/R) injury by upregulating superoxide dismutase (SOD) activity both in serum and brain tissues, simultaneously significantly reducing the levels of malondialdehyde (MDA) and nitric oxide synthase (NOS). Moreover intratympanic delivery did not cause injury of cochlear function by preliminary study on the toxicity. These findings suggested that PLGA NPs-based delivery system via inner ear administration was a promising candidate to brain delivery for the treatment of brain diseases.
研究领域:
药剂学
·
神经科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2023
·
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.
研究领域:
药剂学
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生物材料
·
药物递送
✓ 已验证
产品关联
DOI
高影响因子
Journal of Pharmaceutical Investigation
·
2024
·
IF 5.3
Zhou Limei,Shang Yunxia,Wang Yaru,Wei Xiaohui
Purpose Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease that poses a serious threat to individuals' health and lives. Notoginsenoside R1 (R1) alleviates various symptoms caused by UC effectively. However, the application of R1 is somewhat restricted due to its low bioavailability and nontargeted delivery in vivo. Consequently, it is imperative to develop novel strategies to overcome the aforementioned limitations and enhance the efficacy of this drug. To enhance R1's efficacy and targeting ability, polyethylene glycol poly (lactic-co-glycolic acid) nanoparticles loaded with R1 (R1@PEG–PLGA NPs) modified by transferrin (Tf) were prepared in this study and named R1@Tf–PEG–PLGA NPs. Methods R1@PEG–PLGA NPs and R1@Tf–PEG–PLGA NPs were prepared through nanoprecipitation, and the characterization methods were as follows: First, the surface morphology of the NPs was studied through transmission electron microscopy. Second, particle size, polydispersity index (PDI), and zeta potential were measured with a Malvern particle size analyzer, and the Tf grafting rate on the surface of the NPs was determined by using a bicinchoninic acid protein quantification kit. Third, high-performance liquid chromatography was used in determining the drug load (DL), entrapment efficiency (EE), and in vitro release of the prepared preparation. In addition, the fluorescence intensities of fluorescent-labeled NPs absorbed and ingested in Caco-2 cells were observed through in vitro experiments using fluorescence microscopy; the effects of incubation time, incubation temperature, and endocytosis inhibitors on the uptake of nanoparticles were compared; and the uptake-transport mechanism was explored. Finally, in vivo experiments were performed using the oxazolone (OXZ)-induced UC model in Sprague–Dawley (SD) rats to assess the pharmacodynamic effects and tissue distribution of the prepared NPs. Results The experimentally prepared R1@Tf–PEG–PLGA NPs were round particles with particle size and PDI of 153.50 ± 2.01 and 0.11 ± 0.01, respectively. In addition, the DL of R1@Tf-PEG-PLGA NPs was 24.26% ± 0.18%, and the EE was 50.32% ± 0.86%. Furthermore, R1@Tf–PEG–PLGA NPs had a slower cumulative release rate in vitro than R1 and R1@PEG–PLGA NPs. Fluorescence results showed that under the same conditions, Caco-2 cells took up more Tf-PEG–PLGA NPs than they took up PEG–PLGA NPs. Studies on the cellular uptake mechanism of absorption and uptake determined that the PEG–PLGA NPs entered the cells mainly through fovea-mediated endocytosis, whereas the Tf–PEG–PLGA NPs entered the cells mainly through fovea-mediated and lattice protein-mediated endocytosis. In vivo intestinal tissue distribution results in OXZ-induced SD rats showed that R1@Tf–PEG–PLGA NPs were more enriched in the colon than R1 and R1@PEG–PLGA NPs, and pharmacodynamic evaluation showed that R1@Tf–PEG–PLGA NPs exhibited more pronounced effects in ameliorating colonic injury. Conclusion R1@Tf–PEG–PLGA NPs showed significant colonic targeting and anti-UC effect, showing promising applications.
研究领域:
药学
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纳米技术
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炎症性肠病
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-23
·
IF 12.6
Zou Lan,Wang Rujing,Zhao Mengnan,Li Yuke,Sun Chen,Xie Jinjin,Chen Yan,Jing Qian,Mi Dandan,Shi Sanjun
Pyroptosis, a recently identified cellular demise regulated by gasdermin family proteins, is emerging as a promising avenue in cancer immunotherapy. However, the realm of light-controlled pyroptosis in cancer cells remains largely unexplored. In this study, we took a deliberate approach devoid of any chemical alterations to develop a novel photosensitizer called “pharmaceutical-dots (pharm-dots)” by combining nonemissive polymers (Poly (lactic-co-glycolic acid), PLGA) with nonfluorescent invisible molecules like curcumin, berberine, oridonin into PLGA nanoparticles (PLGA-NPs). Initially, our research commenced with a comprehensive mechanistic comparison study, consolidating fragmented information on optical mechanisms. This exploration revealed that surface passivation atoms play a dominant role in governing the fluorescence emission of PLGA-NPs. Remarkably, these new luminophores, composed of two non-inherently luminous components, exhibit a remarkable synergistic boost in photoluminescence through a “0 + 0 > 2” phenomenon. In-depth investigations uncovered that these luminous PLGA-NPs, capable of generating 1 O 2 , induce pyroptosis under photoexcitation conditions through the caspase-3/gasdermin E (GSDME) pathway. Simultaneously, our findings highlight PLGA-NPs as a novel optical formulation suitable for imaging, displaying substantial biological activity when paired with photoirradiation. This discovery holds the potential to facilitate the application of light-controlled pyroptosis in antitumor therapy, marking a promising stride toward innovative approaches in cancer treatment. Graphical abstract
研究领域:
癌症研究
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生物光子学
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纳米技术
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免疫疗法
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2020
·
IF 3.644
Xiang Yang,Wang Weijia,Gao Yuanhui,Zhang Jianquan,Zhang Jing,Bai Zhiming,Zhang Shufang,Yang Yijun
We successfully fabricated artificial bile duct via 3D printing technique which was composed of poly (lactic-co-glycolic acid) (PLGA) and gelatin methacrylate (GelMA). The PLGA-inner layer provided sufficient strength to support the bile duct contraction, the GelMA-outer layer possessed good biocompatibility to provide a good living environment for the cells. Moreover, IKVAV laminin peptide (Ile-Lys-Val-Ala-Val) and ultrasmall superparamagnetic iron oxide (USPIO) were used to regulate scaffold cell adhesion and magnetic resonance imaging (MRI) detection, respectively. After BMSCs co-culture with IKVAV at a certain concentration, the survival rate and adhesion of BMSCs was increased obviously. Meanwhile, the fabricated scaffold exhibited the tensile modulus in the range of 17.19 – 29.05 MPa and the compressive modulus in the range of 0.042 – 0.066 MPa, which could meet the needs of human implantation. In an animal experiment in vivo pig bile duct regeneration, PLGA/GelMA/IKVAV/USPIO duct conduits could promote bile duct regeneration and enhance cytokeratin 19 (CK19) expression. In summary, the composite bile duct scaffold with excellent MRI imaging function and biocompatibility could be used to develop bioactive artificial bile ducts.
研究领域:
生物医学工程
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组织工程
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再生医学
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医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2018
·
IF 4.432
Juqun Xi,Wenjuan Wang,Lanyue Da,Jingjing Zhang,Lei Fan,Lizeng Gao
Imaging-guided diagnosis and therapy has been highlighted in the area of nanomedicines. However, integrating multiple functions with high performance in one theranostic (“all-in-one”) still presents considerable challenges. Here, “all-in-one” nanoparticles with drug-loading capacity, catalase-mimetic activity, photoacoustic (PA) imaging ability and photothermal properties were prepared by decorating Au nanoparticles on doxorubicin (DOX) encapsulated poly(lactic-co-glycolic acid) (PLGA) vehicle. The results revealed that the as-prepared Au-PLGA hybrid nanoparticles possessed high photothermal conversion efficiency of up to approximately 69.0%, meanwhile their strong acoustic generation endowed them with efficient PA signal sensing for cancer diagnosis. On an 808 nm laser irradiation, the O2 generation, DOX release profile and reactive oxygen species (ROS) level were all improved, which were beneficial to relieving tumor hypoxia and enhanced the cancer chemo/PTT combined therapy. Overall, the multifunctional Au-PLGA hybrid nanoparticles with these integrated advantages shows promise in PA imaging-guided diagnosis and synergistic tumor ablation.
研究领域:
纳米技术
·
癌症研究
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生物医学工程
·
诊疗学
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光热疗法
·
光声成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Yaojie Wei,Zhongqun Liu,Xu Zhu,Le Jiang,Weidong Shi,Yingjin Wang,Nan Xu,Fangli Gang,Xiumei Wang,Lingyun Zhao,Jun Lin,Xiaodan Sun
Peri-implant aseptic inflammation and osteolysis can cause aseptic loosening, leading to the failure of implants. Therefore, aseptic loosening of orthopedic implants remains an imminent problem for the development of durable and effective implants. In this work, a common anti-inflammatory drug (aspirin, ASA) was loaded in poly(lactic-co-glycolic acid) (PLGA) to construct nanofiber coatings on titanium (Ti) via electrospinning. The adhesion of the nanofiber coatings to Ti was ensured by polydopamine (PDA) modification. A stable and sustainable release of aspirin from the nanofiber coatings could last up to 60 days. Such electrospun PLGA@ASA nanofiber coatings could promote proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) as well as inhibit M1 polarization and RANKL-induced osteoclast differentiation of macrophages in vitro . These results indicated that this facile formulation of the PLGA@ASA nanofiber coatings for long-term drug release could be expected to address the problem of aseptic loosening effectively in dual directions of both anti-inflammation and improving osseointegration simultaneously. Notably, the in vivo experiments demonstrated that PLGA@ASA nanofiber coatings did promote osseointegration ability of Ti implants significantly, even in challenging condition with wear particles, and also effectively inhibited Ti particle induced osteolysis around the implants. This work indicates a promising way for the development of durable and effective implants by using PLGA@ASA-PDA-Ti to address the problem of aseptic loosening in dual directions.
研究领域:
生物材料
·
骨科
·
组织工程
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2023
·
IF 3.4
Xiaoyan He,Jiwei Liu,Tao Song,Yiying Sun,Xiaoyan Lu,Nuannuan Li,Kaoxiang Sun
A satisfactory drug release profile for gonadotropin-releasing hormone (GnRH) agonist drugs is high initial release followed by small amount of drug release per day. In the present study, three water-soluble additives (NaCl, CaCl2 and glucose) were selected to improve the drug release profile of a model GnRH agonist drug-triptorelin from PLGA microspheres. The pore manufacturing efficiency of the three additives was similar. The effects of three additives on drug release were evaluated. Under the optimal initial porosity, the initial release amount of microspheres containing different additives was comparable, this ensured a good inhibitory effect on testosterone secretion in the early stage. For NaCl or CaCl2 containing microspheres, the drug remaining in the microsphere depleted rapidly after the initial release. The testosterone concentration gradually returned to an uncontrolled level. However, for glucose containing microspheres, it was found that the addition of glucose could not only increase the initial release of the drug but also assist in the subsequent controlled drug release. A good and long-time inhibitory effect on testosterone secretion was observed in this formulation. The underlying cause why the incorporation of glucose delayed the subsequent drug release was investigated. SEM results showed that considerable pores in glucose containing microspheres were healed during the microspheres incubation. After thermal analysis, an obvious glass transition temperature (Tg) depression was observed in this formulation. As Tg decreased, polymer chains are able to rearrange at lower temperatures. This, morphologic change was reflected in the gradual closure of the pores, and is the likely reason that drug release slowed down after the initial release.HIGHLIGHTSThe addition of glucose could not only increase the burst release of the drug but also delay the subsequent drug release.High initial burst and a sustained drug release helped obtain a good inhibitory effect on testosterone secretion.As Tg decreased, polymer chain was prone to rearrange. Morphologic change was reflected in the gradual closure of the pores. This was the reason that drug release slowed down after the initial burst.
研究领域:
药剂学
·
药物递送系统
·
药理动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Feiyang Jin,Di Liu,Hui Yu,Jing Qi,Yuchan You,Xiaoling Xu,Xuqi Kang,Xiaojuan Wang,Kongjun Lu,Xiaoying Ying,Jian You,Yongzhong Du,Jiansong Ji
Acute lung injury (ALI) is a serious illness without resultful therapeutic methods commonly. Recent studies indicate the importance of oxidative stress in the occurrence and development of ALI, and mitochondria targeted antioxidant has become a difficult and hot topic in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted microsphere (MS) for ALI therapy are developed, with triphenylphosphonium cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically target the mitochondria, increasing the effect of antioxidant. The results manifest that with the increase of microsphere, lung distribution of microsphere is also increased in murine mice, and after SA modification, the microsphere exhibits the ideal lung-targeted characteristic in ALI model mice, due to SA efficiently targeting to E-selectin expressed on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS has better antioxidative capacity, decreases intracellular ROS generation, and increases mitochondrial membrane potential, contributing to a lower apoptosis rate in human umbilical vein endothelial cells (HUVECs) compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has been alleviated markedly and the oxidative stress is ameliorated efficiently. Significant histological improvements by SA/Cur-TPP/MS are further proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a promising drug formulation for ALI therapy.
研究领域:
药学
·
生物医学工程
·
药理学
·
治疗学
·
药物递送系统
·
肺疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 18
·2831-2842
·
IF 4.776
Fen Zhang,Qingtao Li,Zefeng Lin,Limin Ma,Sheng Xu,Qi Feng,Hua Dong,Yu Zhang,Xiaodong Cao
Stem cells are an alternative solution for repairing bone defects. Cell migration and homing from the edge of the defect is important for new bone formation. However, the hostile ischemic environment results in limited migration, homing and survival of stem cells. In this article, ferric hydroxide (Fe(OH)3) nanoparticle-coated poly(lactic-co-glycolic acid) microspheres (FePLGA) were designed via a Pickering emulsion to facilitate stem cell homing. In the process, Fe(OH)3 nanoparticles were immobilized uniformly on the surface of FePLGA microspheres. The morphology, element analysis and Fe content of the FePLGA microspheres were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). Then, these microspheres were sintered to form porous microsphere scaffolds. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was immobilized on the scaffolds via a polydopamine coating to induce osteogenic differentiation. The cell viability, adhesion and migration of mouse bone marrow stromal cells (mBMSCs) cultured on different scaffolds were tested. The results indicated that the mBMSC culture on scaffolds containing Fe(OH)3 nanoparticles exhibited better proliferation, osteoblastic differentiation and migration. Moreover, the iron-containing, rhBMP-2-releasing scaffolds could enhance cell homing efficiency and promote bone formation and osteoconduction when implanted into critical size bone defect models of rabbit femur. Therefore, this new porous PLGA scaffold modified with iron and rhBMP-2 promotes bone repair by recruiting stem cells to the defect site and inside of scaffolds.
研究领域:
材料科学
·
组织工程
·
生物材料
·
再生医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Yinlian Yao,Shilong Fan,Yinqiang Fan,Xin Shen,Xingxing Chai,Yiming Shao,Jiang Pi,Xueqin Huang,Yiming Shao,Zhikun Zhou,Yue Zhao,Hua Jin
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. In vitro data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. In vivo experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.
研究领域:
药理学
·
纳米技术
·
免疫学
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 4
·607-624
·
IF 6.331
Andy Wijaya,Yi Wang,Dan Tang,Yuan Zhong,Boyan Liu,Meng Yan,Quhui Jiu,Wei Wu,Guixue Wang
Nitric oxide (NO) is an exceptional endogenous biological gas that mediates and regulates physiological and pathological processes in the human body. However, its synthesis process is impaired during athero-progression and formation. Hence, a strategy to boost NO production and target endothelial nitric oxide synthase (eNOS) is crucial and intriguing in atherosclerosis (AS) management. Herein, we prepare L-arginine (LA) and lovastatin (LV) co-loaded PLGA nanomedicine to achieve sustainable release for enhancing NO production. The utilization of LA reveals that LA has dual contributions, acting as a NO donor and enhancing the solubility of LV by stabilizing PLGA NPs. PLGA-LA/LV demonstrated its potential to boost NO in vitro and in vivo confirmed using DAF-FM DA, augment eNOS and p-eNOS mRNA and protein levels, and suppress the ki67 proliferation marker in VSMCs; in addition, it lowers the total cholesterol level of blood plasma in C57BL/6 mice. Moreover, PLGA can protect the compound delivered and enhance the bioavailability to reach and get released in the blood circulation after oral administration. Collectively, our results endow a safe and efficient nanomedicine outcome, specifically with potential for AS management.
研究领域:
药学
·
心血管疾病
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）