| Title |
High-efficiency liposomal encapsulation of a tyrosine kinase inhibitor leads to improved in vivo toxicity and tumor response profile
|
|---|---|
| Published in |
International Journal of Nanomedicine, October 2013
|
| DOI | 10.2147/ijn.s51949 |
| Pubmed ID | |
| Authors |
Rajesh Mukthavaram, Pengfei Jiang, Rohit Saklecha, Dmitri Simberg, Ila Sri Bharati, Natsuko Nomura, Ying Chao, Sandra Pastorino, Sandeep C Pingle, Valentina Fogal, Wolf Wrasidlo, Milan Makale, Santosh Kesari |
| Abstract |
Staurosporine (STS) is a potent pan-kinase inhibitor with marked activity against several chemotherapy-resistant tumor types in vitro. The translational progress of this compound has been hindered by poor pharmacokinetics and toxicity. We sought to determine whether liposomal encapsulation of STS would enhance antitumor efficacy and reduce toxicity, thereby supporting the feasibility of further preclinical development. We developed a novel reverse pH gradient liposomal loading method for STS, with an optimal buffer type and drug-to-lipid ratio. Our approach produced 70% loading efficiency with good retention, and we provide, for the first time, an assessment of the in vivo antitumor activity of STS. A low intravenous dose (0.8 mg/kg) inhibited U87 tumors in a murine flank model. Biodistribution showed preferential tumor accumulation, and body weight data, a sensitive index of STS toxicity, was unaffected by liposomal STS, but did decline with the free compound. In vitro experiments revealed that liposomal STS blocked Akt phosphorylation, induced poly(ADP-ribose) polymerase cleavage, and produced cell death via apoptosis. This study provides a basis to explore further the feasibility of liposomally encapsulated STS, and potentially related compounds for the management of resistant solid tumors. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 51 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 27% |
| Student > Bachelor | 7 | 14% |
| Other | 6 | 12% |
| Researcher | 5 | 10% |
| Student > Master | 4 | 8% |
| Other | 3 | 6% |
| Unknown | 12 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 9 | 18% |
| Medicine and Dentistry | 9 | 18% |
| Chemistry | 7 | 14% |
| Immunology and Microbiology | 4 | 8% |
| Biochemistry, Genetics and Molecular Biology | 3 | 6% |
| Other | 6 | 12% |
| Unknown | 13 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 91. 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 08 December 2021.
All research outputs
#466,776
of 25,373,627 outputs
Outputs from International Journal of Nanomedicine
#20
of 4,123 outputs
Outputs of similar age
#3,658
of 219,840 outputs
Outputs of similar age from International Journal of Nanomedicine
#2
of 94 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,123 research outputs from this source. They receive a mean Attention Score of 4.7. This one has done particularly well, scoring higher than 99% of its peers.
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We're also able to compare this research output to 94 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.