MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Wenjing Li,Xinru Li,Yajie Gao,Yanxia Zhou,Shujin Ma,Yong Zhao,Jinwen Li,Yan Liu,Xinglin Wang,Dongdong Yin
The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic–lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.
研究领域:
药学
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药理学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 13
·1825-1837
·
IF 0
Changcan Shi,Fanglian Yao,Jiawen Huang,Guoliang Han,Qian Li,Musammir Khan,Yakai Feng,Wencheng Zhang
Herein, we developed a novel biodegradable gene carrier for rapid endothelialization of endothelial cells (ECs) in vitro. Three triblock amphiphilic copolymers, methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-2,5-morpholinedione-co-glycolide)-graft-polyethyleneimine (mPEG-b-P(MMD-co-GA)-g-PEI) with different 3(S)-methyl-2,5-morpholinedione and glycolide contents were synthesized. Microparticles (MPs) were obtained via self-assembly of these copolymers. The hydrophobic core composed of P(MMD-co-GA) segments provide crosslinking points for numbers of PEG and short PEI chains to form a highly hydrophilic and positively charged corona/shell of MPs. Using these MPs, potential genes (ZNF580) for rapid endothelialization were efficiently transported into EA.hy926 cells. Because of the hydrophilic PEG chains and low molecular weight PEI in the triblock copolymers, the cytotoxicity of these MPs and their complexes with pEGFP–ZNF580 was decreased significantly. The transfection efficacy of MPs/pEGFP–ZNF580 complexes was as high as Lipofectamine™ 2000 reagent to EA.hy926 cells in vitro. The proliferation and migration of EA.hy926 cells were improved greatly by the expression of pEGFP–ZNF580 after 60 hours. Our results indicated that the mPEG-b-P(MMD-co-GA)-g-PEI based MPs could be a suitable non-viral gene carrier for ZNF580 gene to enhance rapid endothelialization.
研究领域:
生物医学工程
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基因治疗
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材料科学
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细胞生物学
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产品关联
DOI
PubMed
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 4
·1-10
·
IF 4.026
Liu Xia,Zhang Mengying,Tian Yuxin,Liu Ruijia,Wang Yunfei,Guo Feifei,Gong Yanling,Yan Meixing
Luteolin (Lu) is a kind of flavonoid that has been proved to treat non-alcoholic fatty liver disease by alleviating intestinal microbiota disorder. In this study, luteolin was coated with methoxy poly(ethylene glycol)–poly(dl-lactide-co-glycolic acid) (mPEG-PLGA) using an emulsion solvent evaporation method, and the optimum preparation process was determined by a single-factor experiment combined with response surface methodology (RSM). Methacrylic acid-methyl methacrylate (1:2) copolymer (Eudragit S100) was then used to coat the surface of Lu/mPEG-PLGA nanoparticles. The physical parameters of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles (Lu-NPs), such as appearance, particle size, potential, particle size distribution and drug release, and stability in vitro, were evaluated. In addition, its cytotoxicity in vitro , pharmacokinetics, tissue distribution, and toxicity in vivo were also studied. The results showed that the prepared Lu-NPs had uniform particle size distribution, high encapsulation efficiency, and good stability. Normal colonic epithelial cells showed good tolerance to Lu-NPs. After oral administration, the blood concentration of luteolin peaked at 8 h, and the main tissue distribution was within the colon, confirming its colon-targeted profile. Safety assessments also indicated that no significant changes were observed in main organs after administration of Lu-NPs. The use of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles is a new strategy for colon-targeted delivery of luteolin that encourages luteolin to fulfill its role in the colon. Graphical abstract
研究领域:
药学
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纳米技术
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药物递送系统
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2021
·
IF 2.882
Shuang Sun,Eryu Shang,Aixia Ju,Yalun Li,Qian Wu,Qiuhong Li,Yang Yang,Yuyan Guo,Dayu Yang,Shaowa Lv
Aim Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii , exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial. Methods A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH 2 ); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm. Results Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo . Fluorescence in vivo endo -microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%. Conclusions Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.
研究领域:
药学
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纳米技术
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qin Chen,Fen-Sheng Qiu,Wei Xie,Wen-Ying Yu,Zhao-An Su,Guang-Ming Qin,You-Kun Kang,Song-Lin Jiang,Chen-Huan Yu
Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum , and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. This encapsulation efficiency was 84.4 ± 6.9 %, and the drug load was 4.02 %±0.35 %. The results showed that GPA-NP displayed more prolonged GPA release and higher bioavailability in vitro than GPA. GPA-NP obviously reduced the levels of oxidative stress markers and inflammatory cytokines in both retinal tissues of DR mice and high glucose-exposed HRMEC better than GPA alone. Mechanismly, GPA blocked the Nrf2-Keap1 interaction by binding with Kelch domain of Keap1 via alkyl and hydrogen bonds. Therefore, GPA-NP exerted more potent protectivity effects against high glucose-induced retinal microvascular endothelial ferroptosis in vitro and in vivo by activating Nrf2/HO-1/GPX4 pathway. It could be a promising therapeutic agent for preventing DR.
研究领域:
药理学
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纳米技术
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糖尿病
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眼科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 25
·20761-20771
·
IF 3.289
Weiwei Zhang,Delong Zhang,Xiaoshan Fan,Guangyue Bai,Yuming guo,Zhiguo Hu
Four new Y-shaped miktoarm amphiphilic copolymers were synthesized by ring-opening polymerization (ROP) and click chemistry. The structure of these copolymers was determined by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The stereocomplexes were prepared by an evaporation method and confirmed by FT-IR, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Further the aggregation behaviors of these synthesized polymers and their stereocomplexes were studied by fluorescence spectroscopy (PL), transmission electron microscopy (TEM) and light scattering (LS). Their critical micelle concentrations (CMC) obtained by PL were 0.005 mg mL−1 for MPEG1.9k–(scPLA4.5k)2 and 0.039 mg mL−1 for MPEG5k–(scPLA4.5k)2. The aggregation morphologies of homochiral copolymers were worm-like aggregates, while for the stereocomplexes, the spherical micelles were visually observed. The biocompatibility of these copolymers and their stereocomplexes was evaluated with relatively lower cytotoxicity. Finally, the release of doxorubicin (DOX) encapsulated into the micelles in buffer at pH 5.4 was faster than that at pH 7.4. This study demonstrates that the DOX-loaded stereocomplex micelles could be a potential carrier for cancer treatments.
研究领域:
高分子科学
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材料科学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Xiaoli Xia,Jian Zhang,Michael Adu‑Frimpong,Xiaoxiao Li,Xinyi Shen,Qing He,Wanjing Rong,Hao Ji,Elmurat Toreniyazov,Ximing Xu,Jiangnan Yu,Qilong Wang
Hyperoside (Hyp) self-assembled polymeric micelles (Hyp-PMs) were purposely developed to enhance aqueous solubility, in vivo availability and anti-oxidative effect of Hyp. In preparing Hyp-PMs, we employed the thin film dispersion method with the micelles consisting of TPGs and mPEG2000-PDLLA3000. The particle size, polydispersity index and zeta potential of Hyp-PMs were 67.42 ± 1.44 nm, 0.229 ± 0.015 and −18.67 ± 0.576 mV, respectively, coupled with high encapsulation efficiency （EE）of 90.63 ± 1.45% and drug loading (DL) of 6.97 ± 1.56%. Furthermore, the value of critical micelle concentration (CMC) was quite low, which indicated good stability and improved self-assembly ability of Hyp-PMs. Also, trend of in vitro Hyp release from Hyp-PMs demonstrated enhanced solubility of Hyp. Similarly, in comparison with free Hyp, oral bioavailability of Hyp-PMs was improved (about 8 folds) whilst half-life of Hyp-PMs was extended (about 3 folds). In vitro anti-oxidative effect showed obvious strong scavenging DPPH capability of Hyp-PMs, which may be attributed to its smaller size and better solubility. Altogether, Hyp-PMs may serve as a possible strategy to potentially enhance aqueous solubility, bioavailability and anti-oxidative effect of Hyp, which may play a key role in Hyp application in the pharmaceutical industries.
研究领域:
药学
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纳米技术
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药物递送系统
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药代动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Xiaoyan Xu,Tianhao Zhou,Xudong Wei,Xuelian Jiang,Jiyan Cao
Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.
研究领域:
肿瘤学
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纳米技术
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分子生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 32
·27102-27112
·
IF 3.289
Lei Li,Beibei Lu,Qikui Fan,Lulu Wei,Jianning Wu,Jun Hou,Xuhong Guo,Zhiyong Liu
In this work, well-defined pH-responsive methoxy poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly[2-(dimethylamino)ethyl methacrylate]-g-7-propinyloxy coumarin triblock amphiphilic copolymers (mPEG-b-PCL-b-PDMAEMA-g-PC) were synthesized using a combination of atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and click chemistry. The chemical structures and compositions of these copolymers were characterized using Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H NMR). The molecular weights of the copolymers were obtained using 1H NMR spectroscopy and gel permeation chromatography (GPC) measurements. Subsequently, the polymers could self-assemble into micelles which were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescence spectroscopy. The pH-responsive self-assembly behavior of these triblock copolymers in water were investigated at different pH values of 5 and 7.4 for controlled doxorubicin release, the results indicated that the release rate of DOX could be effectively controlled by altering the pH, DOX was sealed in neutral surroundings and DOX release was triggered in acidic surroundings. CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the micelles had no associated cytotoxicity, possessed good biodegradability and biocompatibility, and identified the location of the DOX in HeLa cells. The DOX-loaded micelles possessed high cytotoxicity to HeLa cells and exhibited inhibition of the proliferation of HeLa cells. Moreover, these flexible micelles with an on–off switched drug release may offer a promising pattern to deliver a wide variety of hydrophobic payloads to tumor cells for cancer therapy.
研究领域:
材料科学
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纳米技术
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Journal of Macromolecular Science Part A-Pure and Applied Chemistry
·
2019
·
IF 1.163
Xiaodong Zhang,Zuoqian Yu,Feizhao Jiang,Lechi Ye,Jinlei Li,Xingzhao Ye,Chungen Xing
During the healing and reconstruction process of digestive tract, biodegradable anastomat plays an important role. Various of materials have been explored to prepare suitable anastomat. However, the biodegradable ratio or biocompatibility could not meet the requirement of wound healing in clinical application. To overcome these obstacles, we synthetized methoxy-poly(ethylene glycol)-block-polylactide (mPEG-b-PLA) and methoxy-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (mPEG-b-PLGA) with different molecular weight. Biodegradable anastomotic tubes were prepared from these diblock copolymers using electrospinning technique. The thickness of anastomotic tube could be regulated by spinning conditions. Anastomotic tubes had exhibited excellent hemocompatibility (hemolysis ratios were ranged from 0.5% to 1.5%) and cytocompatibility. After 3 days, epithelial cells were adhered closely and covered fully on the surface of nanofibrous tubes. Moreover, mPEG-b-PLGA3 based anastomotic tube had play an important role to improve the healing and reconstruction process of cecal incision. The biodegradable anastomotic tubes from diblock copolymers of mPEG-b-PLA and mPEG-b-PLGA could promote healing and reconstruction of digestive tract and might play an important role after operation.
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DOI
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 3
·
IF 6.353
Wang Qiaoying,Wu Changqiang,Li Xiaoting,Yang Dixiao,Shi Liangjun
We have designed and developed an effective drug delivery system using biocompatible polymer of poly (ethylene glycol)-polyaspartic acid (mPEG-PAsp) for co-loading the chemotherapy drugs paclitaxel (PTX) and cisplatin (CP) in one nano-vehicle. This study aimed to improve the anti-cancer efficacy of combinations of chemotherapy drugs and reduce their side effects. mPEG-PAsp-(PTX/Pt) nano-micelles disperse well in aqueous solution and have a narrow size distribution (37.8 ± 3.2 nm) in dynamic light scattering (DLS). Drug release profiles found that CP released at pH 5.5 was significantly faster than that at pH 7.4. MPEG-PAsp-(PTX/Pt) nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 μg/mL. Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms. Results from our studies suggested that mPEG-PAsp-(PTX/Pt) nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2020
·
IF 2.87
Feng Wang,Youhua Li,Lu Yu,Jinwen Zhu,Fuming Zhang,Robert J. Linhardt
Amphiphilic mPEG-modified peptide nanoparticles were developed from oligo-phenylalanine (OPhe) nanoparticles (NPs) synthesized via papain. Tyndall effects indicate that OPhe NPs are amphiphobic. Addition of protein perturbants, sodium dodecyl sulfate (SDS), and urea, in the dispersion solution of OPhe NPs can significantly reduce the Rh,m value of NPs, from approximately 749.2 nm to about 200 nm. Therefore, the hydrophobic interaction and hydrogen bonding play major roles in maintaining the aggregation of OPhe NPs. Using the “grafting to” method, the methoxypolyethylene-modified OPhe NPs (mPEG-g-OPhe NPs) were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), 1H NMR, electrospray ionization mass spectrometry (ESI-MS), and dynamic light scattering (DLS). The attenuated total reflectance (ATR) spectrum of OPhe NPs and mPEG-g-OPhe NPs demonstrate that the secondary structures of these NPs are mainly β-type. mPEG-g-OPhe NPs can self-aggregate into spherical micelles both in water and cyclohexane. Increasing the chain length of the mPEG moiety, the critical micellar concentrations of mPEG-g-OPhe NPs increased in water but decreased in cyclohexane. The light stability, thermal stability, hydrolysis stability, and encapsulation stability of curcumin were significantly promoted by encapsulation in the micelles formed by mPEG-g-OPhe NPs. The protective effects regularly varied with the variations in the mPEG chain length of mPEG-g-OPhe NPs.
研究领域:
生物化学
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材料科学
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药物递送
✓ 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）