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  1. Article: Combination of miR159 Mimics and Irinotecan Utilizing Lipid Nanoparticles for Enhanced Treatment of Colorectal Cancer.

    Yang, Rulei / Liu, Yiran / Yang, Ning / Zhang, Tian / Hou, Jiazhen / He, Zongyan / Wang, Yutong / Sun, Xujie / Shen, Jingshan / Jiang, Hualiang / Xie, Yuanchao / Lang, Tianqun

    Pharmaceutics

    2024  Volume 16, Issue 4

    Abstract: Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic ... ...

    Abstract Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid nanoparticle (LNP), presents the capability to achieve co-delivery of oligonucleotides and chemotherapeutic drugs for cancer therapy. In this study, we constructed lipid nanoparticles, termed as LNP-I-V by microfluidics to co-deliver oligonucleotides miR159 mimics (VDX05001SI) and irinotecan (IRT), demonstrating effective treatment of CRC both in vitro and in vivo. The LNP-I-V exhibited a particle size of 118.67 ± 1.27 nm, ensuring excellent stability and targeting delivery to tumor tissues, where it was internalized and escaped from the endosome with a pH-sensitive profile. Ultimately, LNP-I-V significantly inhibited CRC growth, extended the survival of tumor-bearing mice, and displayed favorable safety profiles. Thus, LNP-I-V held promise as an innovative platform to combine gene therapy and chemotherapy for improving CRC treatment.
    Language English
    Publishing date 2024-04-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics16040570
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Starburst low-molecular weight polyethylenimine for efficient gene delivery.

    Zhao, Yanjun / Yang, Rulei / Liu, Dong / Sun, Mingjing / Zhou, Lijun / Wang, Zheng / Wan, Ying

    Journal of biomedical materials research. Part A

    2012  Volume 100, Issue 1, Page(s) 134–140

    Abstract: Low-molecular weight polyethylenimine (LMW PEI) shows the advantage of low-cytotoxicity, but has been inefficient in gene delivery as a consequence of the low-charge density. A number of previous studies employed the approach of crosslinking to solve ... ...

    Abstract Low-molecular weight polyethylenimine (LMW PEI) shows the advantage of low-cytotoxicity, but has been inefficient in gene delivery as a consequence of the low-charge density. A number of previous studies employed the approach of crosslinking to solve this problem. In this study, a starburst LMW PEI gene vector has been developed. It has a polyamidoamine (PAMAM) core conjugated with a shell composed of LWM PEI and polyethylene glycol (PEG), that is PAMAM-PEI-PEG. Plasmid DNA (pEGFP-N1) and human cervix epithelial carcinoma (HeLa) cells were used in the study. The results showed that the starburst LMW PEI could effectively condense DNA at N/P above 5. The polyplexes had a size of about 500 nm and a nearly neutral surface because of the PEG shielding effect. This novel gene vector is able to maintain the low-cytotoxicity of LMW PEI, whereas its transfection efficiency was significantly improved.
    MeSH term(s) Cell Survival/drug effects ; Dendrimers/chemical synthesis ; Dendrimers/chemistry ; Dendrimers/pharmacology ; Electrophoresis, Agar Gel ; Gene Transfer Techniques ; Green Fluorescent Proteins/metabolism ; HeLa Cells ; Humans ; Magnetic Resonance Spectroscopy ; Polyethylene Glycols/chemical synthesis ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/pharmacology ; Polyethyleneimine/chemical synthesis ; Polyethyleneimine/chemistry ; Polyethyleneimine/pharmacology
    Chemical Substances Dendrimers ; PAMAM Starburst ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9) ; Polyethylene Glycols (30IQX730WE) ; Polyethyleneimine (9002-98-6)
    Language English
    Publishing date 2012-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2099989-6
    ISSN 1552-4965 ; 1549-3296 ; 0021-9304
    ISSN (online) 1552-4965
    ISSN 1549-3296 ; 0021-9304
    DOI 10.1002/jbm.a.33250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  3. Article ; Online: Biodegradable polymer-curcumin conjugate micelles enhance the loading and delivery of low-potency curcumin.

    Yang, Rulei / Zhang, Suai / Kong, Deling / Gao, Xuli / Zhao, Yanjun / Wang, Zheng

    Pharmaceutical research

    2012  Volume 29, Issue 12, Page(s) 3512–3525

    Abstract: Purpose: To utilize a novel type of polymer-drug conjugate micelle to enhance the delivery of low-potency curcumin.: Methods: Multiple curcumin molecules were conjugated to poly(lactic acid) (PLA) via tris(hydroxymethyl)aminomethane (Tris) linker ... ...

    Abstract Purpose: To utilize a novel type of polymer-drug conjugate micelle to enhance the delivery of low-potency curcumin.
    Methods: Multiple curcumin molecules were conjugated to poly(lactic acid) (PLA) via tris(hydroxymethyl)aminomethane (Tris) linker producing the hydrophobic drug-binding block; methoxy-poly(ethylene glycol) (mPEG) was employed as the hydrophilic block. Micelles were characterized by size, loading capacity, stability, and critical micelle concentration (CMC). Human hepatocellular carcinoma (HepG2) cells were employed to assess cytotoxicity and intracellular targeting ability of micelles.
    Results: mPEG-PLA-Tris-Cur micelles were within nanorange (<100 nm). CMC of such micelles (2.3 ± 0.4 μg/mL) was 10 times lower than mPEG-PLA micelles (27.4 ± 0.8 μg/mL). Curcumin loading in mPEG-PLA-Tris-Cur micelles reached 18.5 ± 1.3% (w/w), compared to traditional mPEG-PLA micelles at 3.6 ± 0.4% (w/w). IC(50) of mPEG-PLA-Tris-Cur micelles (~22 μg/mL at curcumin-equivalent dose) was similar to unmodified curcumin. Placebo and drug-encapsulated conjugate micelles could be efficiently internalized to cytoplasmic compartment of HepG2 cells.
    Conclusions: Micelle-forming polymer-drug conjugates containing multiple drug molecules were an efficient means to increase loading and intracellular delivery of low-potency curcumin.
    MeSH term(s) Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/pharmacology ; Cell Survival/drug effects ; Curcumin/administration & dosage ; Curcumin/pharmacokinetics ; Curcumin/pharmacology ; Drug Carriers/chemistry ; Hep G2 Cells ; Humans ; Micelles ; Neoplasms/drug therapy ; Polyesters/chemistry ; Polyethylene Glycols/chemistry
    Chemical Substances Antineoplastic Agents ; Drug Carriers ; Micelles ; Polyesters ; methoxy poly(ethylene glycol)-poly(lactide) ; Polyethylene Glycols (3WJQ0SDW1A) ; Curcumin (IT942ZTH98)
    Language English
    Publishing date 2012-08-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 843063-9
    ISSN 1573-904X ; 0724-8741 ; 0739-0742
    ISSN (online) 1573-904X
    ISSN 0724-8741 ; 0739-0742
    DOI 10.1007/s11095-012-0848-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1937: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  4. Article ; Online: Pharmacokinetics-Driven Optimization of 4(3 H)-Pyrimidinones as Phosphodiesterase Type 5 Inhibitors Leading to TPN171, a Clinical Candidate for the Treatment of Pulmonary Arterial Hypertension.

    Wang, Zhen / Jiang, Xiangrui / Zhang, Xianglei / Tian, Guanghui / Yang, Rulei / Wu, Jianzhong / Zou, Xiaoli / Liu, Zheng / Yang, Xiaojun / Wu, Chunhui / Shi, Jing / Li, Jianfeng / Suo, Jin / Wang, Yu / Zhang, Rongxia / Xu, Zhijian / Gong, Xudong / He, Yang / Zhu, Weiliang /
    Aisa, Haji Akber / Jiang, Hualiang / Xu, Yechun / Shen, Jingshan

    Journal of medicinal chemistry

    2019  Volume 62, Issue 10, Page(s) 4979–4990

    Abstract: Phosphodiesterase type 5 (PDE5) inhibitors are first-line therapy for pulmonary arterial hypertension (PAH) and erectile dysfunction. As a continuing work to improve the terminal half-lives and oral bioavailabilities of our previously reported 4(3 H)- ... ...

    Abstract Phosphodiesterase type 5 (PDE5) inhibitors are first-line therapy for pulmonary arterial hypertension (PAH) and erectile dysfunction. As a continuing work to improve the terminal half-lives and oral bioavailabilities of our previously reported 4(3 H)-pyrimidones, a pharmacokinetics-driven optimization focusing on the terminal substituent is described. Two major congeneric series of 4(3 H)-pyrimidones, the aminosulfonylphenylpyrimidones and acylaminophenylpyrimidones, were designed, synthesized, and pharmacologically assessed in vitro and in vivo. Among them, compound 15 (TPN171) with subnanomolar potency for PDE5 and good selectivity over PDE6 was finally recognized as a potential drug candidate, and its pharmacokinetic profiles in rats and dogs are significantly improved compared to the starting compound (3). Moreover, TPN171 was proven to exert a longer lasting effect than sildenafil in animal models, providing a foundation for a once-daily oral administration for its clinical use. TPN171 is currently being investigated in a phase II clinical trial for the treatment of PAH.
    MeSH term(s) Animals ; Dogs ; Drug Design ; Female ; Half-Life ; Hypertension, Pulmonary/drug therapy ; Male ; Phosphodiesterase 5 Inhibitors/chemical synthesis ; Phosphodiesterase 5 Inhibitors/pharmacokinetics ; Phosphodiesterase 5 Inhibitors/pharmacology ; Pyrimidines/chemical synthesis ; Pyrimidines/pharmacokinetics ; Pyrimidines/pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Sprague-Dawley ; Sildenafil Citrate/pharmacology ; Structure-Activity Relationship ; Substrate Specificity
    Chemical Substances Phosphodiesterase 5 Inhibitors ; Pyrimidines ; Sildenafil Citrate (BW9B0ZE037)
    Language English
    Publishing date 2019-05-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.9b00123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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