JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2020
·
IF 2.69
Min Wang,Jianghao Zhan,Laijun Xu,Yanjun Wang,Dan Lu,Zhen Li,Jiehua Li,Feng Luo,Hong Tan
Polyurethane nanomicelle is a promising functional drug delivery system. In this work, the polyurethane (P3-PU) was synthesized from PLGA1200-PEG1450-PLGA1200 (P3, a thermosensitive and biodegradable triblock copolymer) and L-lysine ester diisocyanate (LDI). Then, reactive benzaldehyde was further imported to terminate P3-PU to obtain benzaldehyde modified polyurethane (P3-PUDA). The micelles, temperature-sensitive P3-PU nanomicelle and P3-PUDA nanomicelle, were systematically investigated, including the size, stability, temperature sensitivity, drug loading and release behavior, cytotoxic on human hepatocytes (L02), and inhibitory effect on human hepatocellular carcinoma cells (HepG2). The results show the thermosensitive behavior of the micelles can be adjusted by the terminal group. The polyurethane micelles with a uniform size between 20 nm and 30 nm showed excellent stability and good biocompatibility to L02 cells. Besides, in vitro experiments showed that Dox-loaded P3-PUDA micelles exhibited faster and higher release rate at 37 °C and better inhibitory effect on HepG2 than the Dox-loaded P3-PU micelles. Moreover, the achieved benzaldehyde modified polyurethanes also provides various possibilities to adjust further to enlarge its applications. Therefore, the polyurethane micelles will have great potential in the field of drug carriers.
研究领域:
生物材料学
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药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Expert Opinion on Drug Delivery
·
2014
·
IF 4.116
Jinming Zhang,Yingbo Li,Wei Gao,Michael A Repka,Yitao Wang,Meiwan Chen
Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application.Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo.Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat.Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 – ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension.Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Polymers
·
2025
·Vol. 17
·期 5
·574
·
IF 4.9
Lin Fu,Hengxin Ren,Chaoxing Wang,Yaxin Zhao,Bohang Zou,Xiangyu Zhang
Polymer-based drug-controlled release systems offer greater efficacy and potency than conventional therapies. However, prominent drug side effects, lower circulation, and low drug loading capabilities limit their application range. In this work, the combination of Simvastatin (SIV) and Carvacrol (CAV) into PEG-PLGA microspheres (SIV-CAV-PP-MS) was achieved via an emulsification-solvent evaporation technique, resulting in microspheres characterized by high encapsulation efficiency and reduced particle size. In vitro studies demonstrated that the cumulative drug release increased with higher SIV and CAV levels in the release medium, reaching 88.91% and 89.35% at 25 days. Pharmacokinetic analysis revealed that the concentrations of SIV and CAV reached their maximum levels at approximately seven days in the SIV-CAV-PP-MS group, which indicates that using PEG-PLGA as a carrier significantly delays drug release. In vivo, evaluation demonstrated that the SIV-CAV-PP-MS high-dose group and positive drug control group showed reductions in low-density lipoprotein cholesterol levels by 0.39-fold and 0.36-fold compared to the Hyperlipidemia model group, and the addition of CAV significantly enhanced the lipid-lowering effects of SIV. Histological examinations indicated that the SIV-CAV-PP-MS medium-dose group displayed histological features more closely resembling those of normal mice compared to the Simvastatin control group, with a well-organized hepatocyte structure, a significant reduction in lipids, and improved liver health. The prepared polymeric microsphere utilizing SIV and SAV will be a promising dosage form for hyperlipidemia disease patients, with superior lipid-lowering efficacy and improved patient compliance.
研究领域:
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCES IN POLYMER TECHNOLOGY
·
2020
·
IF 1.539
Lei Li,Yan Li,Cheng Miao,Rui Liu
This study was to explore the therapeutic effect and mechanism of puerarin (PUE) combined with PEGylated nanoparticles on a rat cerebral infarction cell model. In this context, PEG-PLGA/PUE nanoparticles were prepared by the thin-film hydration method, and the toxicity of PEG-PLGA/PUE nanoparticles to brain capillary endothelial cell (BCEC) was detected by MTT. The BCEC/TF cell model was obtained by induction of BCEC cells with TNF-α. The BCEC/TF cell model was identified by immunofluorescence; the protein expression was detected by western blotting; the expression level of miR-424 in cells was measured by RT-qPCR; the targeting relationship between miR-424 and PDCD4 was confirmed by dual-luciferase reporter assay. We found that PEG-PLGA/PUE nanoparticles prepared by the thin-film hydration method had uniform particle size, regular shape, and good stability and were not toxic to cells. The vWF was widely expressed in the cytoplasm in BCECs. The BCEC/TF cell model was obtained after TNF-α treatment, and tissue factor (TF) was widely expressed on the cell membrane of BCEC/TF cells. Furthermore, it was observed that the PEG-PLGA/PUE nanoparticles showed better therapeutic effect on the BCEC/TF cell model than PUE. PEG-PLGA/PUE nanoparticles and PUE inhibited the expression of PDCD4 protein by increasing the expression of miR-424 in BCEC/TF cells. In summary, the therapeutic effect of PEG-PLGA/PUE nanoparticles on the in vitro cell model of cerebral infarction is better than that of PUE. Moreover, PEG-PLGA/PUE inhibits the expression of PDCD4 protein by lowering the expression level of miR-424 in cells, thereby reducing the hazard of cerebral infarction.
研究领域:
药理学
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神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chenchen Bi,Aiping Wang,Yongchao Chu,Sha Liu,Hongjie Mu,Wanhui Liu,Zimei Wu,Kaoxiang Sun,Youxin Li
Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.
研究领域:
药剂学
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神经科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2019
·
IF 4.462
Dinglingge Cao,Xingxian Zhang,MD. Akabar,Yuan Luo,Hao Wu,Xue Ke,Tianyuan Ci
The aim of this research is to utilize a hybrid system of liposomal doxorubicin (DOX-Lip) loaded thermogel (DOX-Lip-Gel) to realize the steady sustained delivery of doxorubicin (DOX), a small hydrophilic drug, for the treatment of breast cancer locally. Herein, liposomal doxorubicin was prepared via the traditional film dispersion method with the particle size of 75 nm and drug entrapment efficiency of 86%. And, the triblock copolymer of poly (D, L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D, L-lactide -co-glycolide) (PLGA-PEG-PLGA) was synthesized via ring-opening polymerization to prepare the thermosensitive hydrogel through dissolving the polymers in DOX-Lip solution. The liposome loaded hydrogel was in a sol state at room temperature and converted into the gel state at body temperature and would degrade gradually during the time in vivo. The drug release of DOX out of DOX-Lip-Gel could be in a steady sustained manner up to 11 days without significant burst release as compared to that of DOX-loaded hydrogel (DOX-Gel). An orthotopic breast cancer model was adopted to evaluate the in vivo antitumor efficacy. And, the results revealed DOX-Lip-Gel had better antitumor efficiency as well as lower side effects.
研究领域:
药剂学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2018
·Vol. 8
·期 5
·1090-1102
·
IF 3.395
Xie Yonghui,Liu Chenchen,Huang Hongwei,Huang Jian,Deng Aiping,Zou Ping,Tan Xueying
This study aimed to investigate the improved therapeutic efficacy and pharmacokinetic profiles of simvastatin (SIM) with imparted bone targeting potential using tetracycline-mediated PEG-PLGA (TC-PEG-PLGA) micelles in osteoporotic rats. The SIM-loaded TC-PEG-PLGA (TC-PEG-PLGA/SIM) micelles were evaluated for particle size, morphology, stability, loading efficiency, cell viability, bone mineral binding ability in vitro, mineralization, pharmacokinetics, and pharmacodynamics. TC-PEG-PLGA conjugates were successfully and could self-assembly form micelles in aqueous medium with a 19.4 μg/mL critical micelle concentration. Then, TC-PEG-PLGA/SIM micelles were prepared with solvent diffusion method, and the obtained micelles (56.21 ± 7.39 nm average size; 81.8 ± 3.1% encapsulation efficiency; and 7.56 ± 0.27% drug loading) led to the prolonged release of SIM from micelles. Cellular uptake test indicated that TC had no effects on micellar internalization and micellar internalization was mainly involved with clathrin-mediated endocytic pathway. In vivo pharmacokinetic results indicated that TC-PEG-PLGA/SIM micelles exhibited a significantly prolonged time in systemic circulation and were preferentially accumulated in bone tissue. TC-PEG-PLGA/SIM micelles showed better therapeutic effects, as reflected by the improved bone mineral density, bone mineral content, and bone mechanical strength. Overall, these results suggested that TC-PEG-PLGA/SIM micelles provide several advantages, including prolonged systemic circulation, enhanced bone tissue distribution, and improved therapeutic outcomes in osteoporotic rats.
研究领域:
药剂学
·
骨科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2023
·
IF 2.9
Weiqian Wu,Ruilai Liu,Jiahao Guo,Zhihuan Hu,Chenjing An,Yan Zhang,Tengyuan Liu,Lian Cen,Yukun Pan
The high hydrophobicity and low oral availability of immunosuppressive drug, rapamycin, seriously limit its application. It was thus aimed to develop a PEG-PLGA based nano-loading system for rapamycin delivery to achieve improved bioavailability with sustained effects via a novel microfluidic chip and manipulation of the hydrophobic PLGA chain length. PDMS based microfluidic chip with Y shape was designed and PEG-PLGA polymers with different PLGA chain length were used to prepare rapamycin nano-delivery systems. Dendritic cells were selected to evaluate the immunosuppressive effect of the nanoparticles including cytotoxicity assay, dendritic cell activation, and cytokine levels. The effects of different PEG-PLGA nanoparticles on the immunomodulatory properties were finally compared. It was shown that PEG-PLGA could be successfully used for rapamycin encapsulation via microfluidics to obtain nano-delivery systems (Rapa&P-20 k, Rapa&P-50 k and Rapa&P-95 k) ranging from 100 nm to 116 nm. The encapsulation efficiency was ranged from 69.70% to 84.55% and drug loading from 10.45% to 12.68%. The Rapa&P-50 k (PLGA chain length: 50 k) could achieve the highest drug loading (DL) and encapsulation efficiency (EE) as 12.68% and 84.55%. The encapsulated rapamycin could be gradually released from three nanoparticles for more than 1 month without any noticeable burst release. The Rapa & P nanoparticles exhibited enhanced immunosuppressive effects over those of free rapamycin as shown by the expression of CD40 and CD80, and the secretion of IL-1β, IL-12 and TGF-β1. Rapa&P-50 k nanoparticles could be the optimal choice for rapamycin delivery as it also achieved the most effective immunosuppressive property. Hence, this study could provide an efficient technology with superior manipulation to offer a solution for rapamycin delivery and clinical application.
研究领域:
药学
·
纳米技术
·
免疫学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Li Piao,Peng Xiang,Yangyang Zhou,Wei Zhao,Ting Yang,Shan Xia,Guanghui Gao,Kexin Chen,Dan Li
Overexpression of epidermal growth factor receptor (EGFR) in cancer is a key cause of recurrence of cervical cancer (CC). Although the EGF-EGFR pathway has been studied for decades, preventing tumor growth and recurrence caused by peripheral EGF remains a great challenge. In this work, a strategy is proposed to reduce the stimulation of high concentration EGF on tumor growth by using a thermo-sensitive hydrogel. The hydrogel is a triblock copolymer composed of polyethylene glycol (PEG) and poly (lactide glycolide) (PLGA). Based on the excellent temperature sensitivity, carrier capacity, swelling property and biocompatibility, the hydrogel can absorb the liquid around the tumor by injection and release EGF continuously at low concentration. The inhibitory effect of hydrogel on tumor growth is fully confirmed by an implanted tumor mouse model with human cervical cancer cell lines (HeLa) using triple-immunodeficient NCG mice. Compared with free EGF, the EGF-loaded hydrogel can hardly induce surface plasmon resonance (SPR) response, which proves that hydrogel can effectively weaken cytoskeleton rearrangement and inhibit cell migration by continuously releasing low concentration EGF. In addition, the EGF-loaded hydrogel can reduce cell proliferation by delaying the progress of cell cycle progression. Taken together, the hydrogel can effectively protect tumor microenvironment from the stimulation of high concentration EGF, delay cancer cellular processes and tumor growth, and thus providing an approach for inhibiting tumor recurrence of CC.
研究领域:
肿瘤学
·
药剂学
·
生物材料
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2019
·Vol. 37
·期 6
·548-559
·
IF 2.804
Xu Wei-Ke,Tang Jing-Yu,Yuan Zhang,Cai Cai-Yun,Chen Xiao-Bin,Cui Shu-Quan,Liu Peng,Yu Lin,Cai Kai-Yong,Ding Jian-Dong
Bacterial infection is a very troublesome issue in wound treatment, which stimulates exudate formation and severely delays the healing process. Herein, a thermogelling dressing system composed of two triblock copolymers of poly(D,L-lactic acid- co -glycolic acid)- b -poly(ethylene glycol)- b -poly(D,L-lactic acid- co -glycolic acid) (PLGA-PEG-PLGA) with different block lengths was developed to deliver teicoplanin (TPN), a glycopeptide antibiotic, for cutaneous wound repair. The TPN-loaded thermogel was a free-flowing sol at room temperature and formed a semi-solid gel at physiological temperature. In vitro studies demonstrated that the TPN-loaded thermogel system exhibited desired tissue adhesiveness and realized the sustained release of TPN in a fast-followed-slow manner for over three weeks. Furthermore, a full-thickness excision wound model in Sprague-Dawley (SD) rats was constructed to assess the efficacy of TPN-loaded thermogel formulation. Gross and histopathologic observations implied that treatment with the thermogel formulation reduced inflammation response, promoted disposition of collagen, enhanced angiogenesis, and accelerated wound closure and maturity of SD rats. The combination of the bioactivity of TPN and the acidic nature of the thermogel matrix was responsible for such an enhanced wound healing process. Consequently, the TPN-loaded PLGA-PEG-PLGA thermogel is a good candidate of wound dressing for full-thickness excision wound healing.
研究领域:
药学
·
生物医学工程
·
伤口护理
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药物递送系统
·
材料科学
✓ 已验证
产品关联
DOI
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
·
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
·
纳米技术
·
炎症性肠病
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）