| Title |
Matrix Metalloproteinase Responsive Delivery of Myostatin Inhibitors
|
|---|---|
| Published in |
Pharmaceutical Research, September 2016
|
| DOI | 10.1007/s11095-016-2038-6 |
| Pubmed ID | |
| Authors |
Alexandra C. Braun, Marcus Gutmann, Regina Ebert, Franz Jakob, Henning Gieseler, Tessa Lühmann, Lorenz Meinel |
| Abstract |
The inhibition of myostatin - a member of the transforming growth factor (TGF-β) family - drives regeneration of functional skeletal muscle tissue. We developed a bioresponsive drug delivery system (DDS) linking release of a myostatin inhibitor (MI) to inflammatory flares of myositis to provide self-regulated MI concentration gradients within tissues of need. A protease cleavable linker (PCL) - responding to MMP upregulation - is attached to the MI and site-specifically immobilized on microparticle surfaces. The PCL disintegrated in a matrix metalloproteinase (MMP) 1, 8, and particularly MMP-9 concentration dependent manner, with MMP-9 being an effective surrogate biomarker correlating with the activity of myositis. The bioactivity of particle-surface bound as well as released MI was confirmed by luciferase suppression in stably transfected HEK293 cells responding to myostatin induced SMAD phosphorylation. We developed a MMP-responsive DDS for MI delivery responding to inflammatory flare of a diseased muscle matching the kinetics of MMP-9 upregulation, with MMP-9 kinetics matching (patho-) physiological myostatin levels. ᅟ: Graphical Abstract Schematic illustration of the matrix metalloproteinase responsive delivery system responding to inflammatory flares of muscle disease. The protease cleavable linker readily disintegrates upon entry into the diseased tissue, therby releasing the mystatin inhibitor. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 25% |
| Taiwan | 1 | 25% |
| Norway | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 38% |
| Student > Bachelor | 6 | 23% |
| Researcher | 2 | 8% |
| Student > Master | 2 | 8% |
| Professor | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 5 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 23% |
| Agricultural and Biological Sciences | 5 | 19% |
| Medicine and Dentistry | 5 | 19% |
| Psychology | 1 | 4% |
| Sports and Recreations | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 7 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 September 2016.
All research outputs
#13,479,192
of 22,888,307 outputs
Outputs from Pharmaceutical Research
#2,112
of 2,860 outputs
Outputs of similar age
#169,480
of 321,980 outputs
Outputs of similar age from Pharmaceutical Research
#14
of 23 outputs
Altmetric has tracked 22,888,307 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,860 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 321,980 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.