Abstract：
:Metformin is an antidiabetic drug which possesses antiproliferative activity in cancer cells when administered at high doses, due to its unfavorable pharmacokinetics. The aim of this work was to develop a pharmacological tool for the release of metformin in proximity of the tumor, allowing high local concentrations, and to demonstrate the in vivo antitumor efficacy after a prolonged metformin exposition. A 1.2% w/w metformin thermoresponsive parenteral formulation based on poloxamers P407 and P124, injectable at room temperature and undergoing a sol-gel transition at body temperature, has been developed and optimized for rheological, thermal and release control properties; the formulation is easily scalable, and proved to be stable during a 1-month storage at 5 °C. Using NOD/SCID mice pseudo-orthotopically grafted with MDA-MB-231/luc+ human breast cancer cells, we report that multiple administrations of 100 mg of the optimized metformin formulation close to the tumor site cause tissue accumulation of the drug at levels significantly higher than those observed in plasma, and enough to exert antiproliferative and pro-apoptotic activities. Our results demonstrate that this formulation is endowed with good stability, tolerability, thermal and rheological properties, representing a novel tool to be pursued in further investigations for adjuvant cancer treatment.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Baldassari S,Solari A,Zuccari G,Drava G,Pastorino S,Fucile C,Marini V,Daga A,Pattarozzi A,Ratto A,Ferrari A,Mattioli F,Barbieri F,Caviglioli G,Florio Tdoi
10.1038/s41598-018-22054-wsubject
Has Abstractpub_date
2018-03-02 00:00:00pages
3929issue
1issn
2045-2322pii
10.1038/s41598-018-22054-wjournal_volume
8pub_type
杂志文章abstract：:The Transient Receptor Potential vanilloid 4 ion channel (TRPV4) is an important sensor for osmotic and mechanical stimuli in the musculoskeletal system, and it is also involved in processes of nociception. In this study we investigated the putative role of TRPV4 ion channels in joint pain. In anesthetized rats we rec...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-47342-x
更新日期：2019-07-29 00:00:00
abstract：:Developmental changes in salamander skulls, before and after metamorphosis, affect the feeding capabilities of these animals. How changes in cranial morphology and tissue properties affect the function of the skull are key to decipher the early evolutionary history of the crown-group of salamanders. Here, 3D cranial b...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-10553-1
更新日期：2017-08-31 00:00:00
abstract：:We propose a novel method to achieve tunable plasmon focusing in graphene/photonic-crystal hybrid structure exhibiting all-angle negative refraction at terahertz frequencies. A two-dimensional photonic crystal composed of a square lattice of dielectric rods is constructed on the substrate of a graphene sheet to provid...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep41788
更新日期：2017-02-02 00:00:00
abstract：:Systemic Sclerosis (SSc) is a disease with limited therapeutic possibilities. Mesenchymal stem cells (MSCs)-therapy could be a promising therapeutic option, however the ideal MSCs source has not yet been found. To address this problem, we perform comparison between bone marrow (BM)-MSCs and adipose (A)-MSCs, by the mi...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-43638-0
更新日期：2019-05-09 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Scientific reports
pub_type： 已发布勘误
doi：10.1038/s41598-020-76567-4
更新日期：2020-11-05 00:00:00
abstract：:We report the results of an experiment on radio-tracking of individual grey field slugs in an arable field and associated data modelling designed to investigate the effect of slug population density in their movement. Slugs were collected in a commercial winter wheat field in which a 5x6 trapping grid had been establi...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-74643-3
更新日期：2020-10-21 00:00:00
abstract：:Magnetic skyrmions are topological quasiparticles of great interest for data storage applications because of their small size, high stability, and ease of manipulation via electric current. However, although models exist for some limiting cases, there is no universal theory capable of accurately describing the structu...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-22242-8
更新日期：2018-03-13 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-73250-6
更新日期：2020-10-01 00:00:00
abstract：:Understanding the chemical and physical properties of metal/graphene oxide (M/GO) interfaces is important when GO is used in electronic and electrochemical devices because the metal layer must be firmly attached to GO. Here, permeation of metal from the surface into GO paper bulk at the M/GO interface was observed at ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep03647
更新日期：2014-01-13 00:00:00
abstract：:Secondhand smoke (SHS) has been associated with a variety of adverse health outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary disease). One way to detect SHS exposure is to measure the concentration of cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed a method...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep03864
更新日期：2014-01-27 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-021-81532-w
更新日期：2021-01-21 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-79238-6
更新日期：2020-12-17 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-19478-9
更新日期：2018-01-24 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-021-81748-w
更新日期：2021-01-26 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-10841-w
更新日期：2017-09-04 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-15148-4
更新日期：2017-11-09 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep39622
更新日期：2016-12-23 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep27089
更新日期：2016-06-02 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-00147-2
更新日期：2017-03-03 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-53982-w
更新日期：2019-11-27 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-75415-9
更新日期：2020-10-26 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-80911-z
更新日期：2021-01-26 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-61450-z
更新日期：2020-03-10 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2017-11-01 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep44217
更新日期：2017-03-13 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-37085-6
更新日期：2019-01-24 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep12720
更新日期：2015-07-30 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-34934-2
更新日期：2018-11-16 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep14821
更新日期：2015-10-07 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-45751-6
更新日期：2019-06-27 00:00:00
