POLYMER BULLETIN
·
2012
·Vol. 69
·期 5
·597-620
·
IF 1.532
Luo Yan-Ling,Yu Wei,Xu Feng
pH-sensitive hydrophilic poly(methacrylic acid)- b -poly(ethylene glycol)- b -poly(methacrylic acid) (PMAA- b -PEG- b -PMAA) triblock copolymers were synthesized through atom transfer radical polymerization, and were characterized by FT-IR, 1 H NMR, and GPC. The as-synthesized polymers can self-assemble into stable and almost spherical nanomicelles in aqueous solution with an average size range from 18 to 89 nm, depending on the micellar concentrations, while they assumed well-defined spherical morphologies in PBS solutions. The micellization behavior in different media was investigated by a fluorescence spectroscopy technique, UV–Vis transmittance, and dynamic light scattering measurements. The critical micelle concentration and size of the micelles decrease with the increasing the length or molecular weights of PEG and PMAA chains. A pH-dependent phase transition behavior produces at a pH value of about 5.2, and the stable pH micellization behavior varied within a narrow pH range from ca. 4.8 to 7.4. These triblock copolymers are generally low cytotoxicity at a micellar concentration below 400 mg L −1 , as revealed by the MTT assay. The prednisone release and release kinetics studies disclosed that these pH-sensitive polymeric micelles are good carriers for the drug delivery.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
BRAIN RESEARCH
·
2023
·
IF 2.9
Yao Wang,Shate Xiang,Mengge Zhang,Jingjing Zhang,Xinghong Ding
Prednisone acetate (PA) has many adverse side effects despite the fact that oral administration of PA is widely administrated in the clinic. However, it is unknown whether PA can cause hippocampal long-term potentiation (LTP) impairment. Therefore, in our study, PA (5 mg/kg·d) through intragastric administration (gavage) was applied to establish a model of impaired hippocampal LTP in C57BL/6 mice, and the method was evaluated by comparing with another method to establish LTP impairment through subcutaneous injection of corticosterone (CORT, 50 mg/kg·d). First, our results showed PA caused a more significant decrease in population spike (PS, %) after high-frequency stimulation (HFS) than CORT, demonstrating PA induced impairment of hippocampal LTP more successfully than CORT. Second, PA caused poorer performance of memory than CORT. Third, PA caused more serious lesions and loss of the granule cell in the dentate gyrus than CORT. Finally, PA caused lower levels of glutamic acid (Glu), N -methyl- d -aspartate receptors (NMDARs) and gamma-aminobutyric acid (GABA) than CORT. All in all, PA (5 mg/kg·d) through intragastric administration (gavage) induced LTP impairment in the hippocampus more successfully than CORT. The neuronal lesions in the dentate gyrus and the consequent decrease of Glu and NMDARs (especially NMDAR2A) may be the cause of LTP impairment.
研究领域:
神经科学
·
药理学
·
行为科学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2013
·
IF 2.108
Yan-Ling Luo,Rui-Juan Huang,Li-Li Zhang,Feng Xu,Ya-Shao Chen
A thermo- and pH-stimuli-responsive brush-shaped graft copolymer based on macromonomers acrylate terminated PMAA–CH=CH 2 and PNIPAAm–CH=CH 2 was synthesized, which is composed of poly(methacrylic acid) (PMAA) and poly( N -ispropylacrylamide) (PNIPAAm) as graft brushes, named PMAA- b -PNIPAAm. The copolymers can self-assemble to form spherically-shaped core-shell nanostrucrued micelles in different media, with the critical micelle concentration (CMC) in aqueous solution from 9.24 to 32.81 mg L −1 , and the hydrodynamic diameters varying with pH and temperature, from 120 to 195 nm. The resultant nanoscale copolymer micelles exhibited pH-triggered thermoresponsive behavior, with low critical solution temperature (LCST) about 38.2–47.5 °C. The polymer micelle nanoparticles were observed to be stable under simulated physiological conditions. The cytotoxicity studies by MTT assay and in vitro prednisone drug release demonstrated that the PMAA- b -PNIPAAm copolymer micelles were not directly toxic to L929 mouse embryonic fibroblasts and the in vitro release behavior under various physiological environments depended upon pH and temperature change. Therefore the as-prepared brush-shaped graft copolymer micelle nanoparticles may serve as a promising “intelligent” drug delivery carrier.
研究领域:
材料科学与工程
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2013
·
IF 2.206
Yan-Ling Luo,Li-Li Chen,Yan Miao,Feng Xu
Novel AB4-type polyurethane (PU) micelle-like amphiphilic block copolymers consisting of hydroxyl-functionalized carboxyl-terminated poly(butadiene-co-acrylonitrile) (f-CTBN) as the hydrophobic cores and methoxy poly(ethylene glycol) (MPEG) as the hydrophilic branched blocks were synthesized via esterification, followed by coupling reaction. Their chemical structure and molecular weight were characterized by FTIR, NMR, and SEC measurements. The block copolymers could easily self-assemble to form core–shell micelle nanoparticles in various media. The micelles bear a critical micelle concentration (CMC) in a range from 0.740 to 6.310 mg L–1 and were very stable even in PBS solutions. The TEM and DLS findings revealed that the micelles were almost spherical and narrow-size-distribution, with TEM mean diameters from 13 to 24 nm, and average hydrodynamic diameter about 124–151 nm. All these depended on chain lengths and compositional ratios of hydrophilic MPEG blocks. The drug loading and in vitro release indicated that the self-assembled micelle nanoparticles could effectively load hydrophobic prednisone, with encapsulation capacity of about 27–30%, and the drug release from the nanoparticles was dependent on MPEG chain lengths and the molar ratios of f-CTBN to MPEG. Cytotoxicity assays disclosed that the as-prepared block copolymer micelle nanoparticles exhibit good biocompatibility and could be employed as potential drug controlled release carriers.
研究领域:
生物材料
·
药物递送
·
纳米医学
·
高分子化学
·
药剂学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Li Qianqian,Zhou Jia,Zhang Dingyi,Zhang Xiafeng,Xu Zhenghao,Wu Dehong
Glucocorticoids (GCs) are commonly used to treat systemic lupus erythematosus (SLE). Unfortunately, excessive GCs can induce many side effects associated with disordered fatty acid (FA) metabolism. Although an increased level of total FA has been found after GCs treatment, it is not clear whether all FA species increased or only certain FA species were altered. A gas chromatography–mass spectrometry-based FA profiling approach was performed to reveal the alterations of FA species in SLE model mice (MRL/lpr) after treatment with 5 mg/kg of prednisone. The study showed a distinct FA profile in MRL/lpr mice compared to the controls, mainly manifested by elevated polyunsaturated FAs (arachidonate, docosahexaenoate, etc.), which are related to the inflammatory state; and altered (product FA/precursor FA) ratios representing the estimated activities of FA desaturase and elongase (higher activities of multiple elongases, △4 desaturase, △5 desaturase, △6 desaturase, and lower activity of △8 desaturase). Treatment with 5 mg/kg of prednisone decreased the total level of n-6 polyunsaturated FA in MRL/lpr mice; in particular, the level of arachidonate and estimated activity of △5 desaturase were reduced to the control level. Moreover, prednisone induced additional perturbations in FAs, including not only saturated FAs, but also monounsaturated FAs and n-3 polyunsaturated FAs, indicating that there was a strong effect of prednisone on FA metabolism. These results may be valuable for further studies of the side effects of GCs treatment.
研究领域:
免疫学
·
药理学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2023
·Vol. 28
·期 1
·1-9
·
IF 4.2
Yan Xiang,Zhang Yayue,Lang Haiyan,Huang Ziming,Chen Xinyi,He Hao,Zhao Qian,Wang Jun
RationaleImmune thrombocytopenia (ITP) is thought to be a result of immune dysfunction, which is treated by glucocorticoids such as prednisone. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) have immunomodulatory properties, but their role in intestinal immune control is unclear. The major goal of this study was to look at the effects of prednisone on platelet, VIP, and PACAP levels in ITP mice, as well as the regulatory system that controls intestinal immunity.Methods Eighteen BALB/c mice were randomly divided into three groups: blank control group, model control group, and prednisone group, with six mice in each group. The ITP animal model control group and the prednisone group were injected with anti-platelet serum (APS) to replicate the ITP animal model. The prednisone group began prednisone intervention on the 8th day. Platelet count was dynamically measured before APS injection, on the 4th day of injection, on the 1st day of administration, on the 4th day of administration, and at the end of the experiment. After the experiment, the expression of p53 protein in mouse mesenteric lymph node lymphocytes was detected by immunohistochemistry. The changes in lymphocyte apoptosis rate in mouse mesenteric lymph nodes were detected by in situ terminal transferase labeling (TUNEL). The contents of VIP and PACAP in the mouse brain, colon, and serum were detected by enzyme-linked immunosorbent assay (ELISA). The contents of IFN-γ, IL-4, IL-10, IL-17A in the mouse spleen were detected by ELISA.Results ①Changes of peripheral platelet count: there was no significant difference in platelet count among the three groups before modeling; on the 4th day, the platelet count decreased in the model control group and prednisone group; on the 8th day, the number of platelets in model control group and prednisone group was at the lowest level; on the 12th day, the platelet count in prednisone group recovered significantly; on the 15th day, the platelet count in prednisone group continued to rise. ②Changes of VIP, PACAP: compared with the blank control group, VIP and PACAP in the model control group decreased significantly in the brain, colon, and serum. Compared with the model control group, the levels of VIP and PACAP in the brain, colon, and serum in the prednisone group were increased except for serum PACAP. ③Changes of mesenteric lymphocytes: the expression of p53 protein in the mesenteric lymph nodes of model control group mice was significantly higher than that of blank control group mice. After prednisone intervention, the expression of p53 protein decreased significantly.④Changes of cytokines in spleen: compared with blank control group, IFN- γ, IL-17A increased and IL-4 and IL-10 decreased in model control group. After prednisone intervention, IFN- γ, IL-17A was down-regulated and IL-4 and IL-10 were upregulated.Conclusion sPrednisone-upregulated VIP and PACAP levels decreased P53 protein expression and apoptosis rate in mesenteric lymph node lymphocytes and affected cytokine expression in ITP model mice. Therefore, we speculate that the regulation of intestinal immune function may be a potential mechanism of prednisone in treating ITP.
研究领域:
免疫学
·
药理学
·
血液学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 9
·2343
·
IF 3.098
Huijuan Wang,Tingting Feng,Donggui Guo,Min Zhang,Lin Chen,Ying Zhou
Sanggenon C (SC), which is a natural flavonoid found in the stem bark of Cortex Mori, has been discovered to have the antioxidant, anti-inflammatory, and antitumor properties. However, its effect in osteoporosis has not yet been reported. In this research, the effect of SC on the proliferation of MC3T3-E1 cells was evaluated by using the MTT assay. Alkaline phosphatase (ALP) activity and the mRNA expression ofRunx2,Collagen I,OPG, andRANKLwere examined. TRAP-positive cell counting and bone resorption pits were adopted to observe the effect of SC on the formation and function of osteoclasts. Next, the mRNA level ofTRAP,CTSK,NFATc1, andTRAF6of osteoclasts were measured by real-time qPCR. In addition, the anti-osteoporosis activity of SC in vivo was evaluated in the zebrafish model. Our study indicated that SC exhibited a significant stimulatory effect on MC3T3-E1 cell proliferation at 1 to 10 μM and caused an increase in ALP activity at 0.3 to 10 μM. It could upregulate the expression ofRunx2,Collagen I, and increases theOPG/RANKL ratio. Furthermore, SC was found to inhibit the formation and function of osteoclasts, which is demonstrated by a lower number of TRAP-positive multinuclear cells and a fewer area of bone resorption pits compared to the control group.TRAP,CTSK, andNFATc1were downregulated in 0.3 to 10 μM SC treated groups. In addition, 3 to 10 μM SC also inhibited the expression ofTRAF6mRNA. When prednisone-induced zebrafish was treated with 0.3, 1, 3, and 10 μM SC, higher mineralization of vertebrate column was discovered in a dose-dependent pattern, which suggests that SC could reverse the bone loss of zebrafish caused by prednisone. In summary, these findings indicated that SC has the potential to prevent or treat osteoporosis.Keywords:Sanggenon C;osteoblast;osteoclast;osteoporosis;zebrafish
研究领域:
药理学
·
生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS
·
2013
·
IF 2.207
Feng Xu,Ting-Ting Yan,Yan-Ling Luo
Novel amphiphilic block copolymers consisting of hydrophobic poly(D,L-lactide) segments and hydrophilic poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide) blocks were designed and synthesized through a simple free radical copolymerization route based on a bifunctional initiator, followed by the ring-opening polymerization of D,L-lactide. The copolymers self-assembled into thermosensitive spherical-nanosized core–shell micelles in aqueous solution in the presence or the absence of the model drug prednisone. The chemical and physical characterizations of drug-loaded and unloaded micelles revealed a lower critical solution temperature of 40°C–47°C, and a critical micelle concentration less than 7.20 mg L−1, a transmission electron microscope mean particle size from 50 to 75 nm, and a narrow dynamic light scattering diameter below 180 nm. The prepared blank and drug-loaded micellar nanoparticles were thermodynamically stabile and employed in targeted drug delivery by responding to the higher temperature of the local microenvironment. Based on prednisone release kinetic studies, structural changes of the self-assembled micelles as well as temperature- or environment-induced diffusion controlled drug release and improved bioavailability. The copolymer micelles exhibited good biocompatibility as established by the MTT cytotoxicity assay. Therefore, an effective target therapy against lesion tissues is feasible using these polymeric micelles.
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）