| Title |
Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model
|
|---|---|
| Published in |
International Journal of Nanomedicine, February 2017
|
| DOI | 10.2147/ijn.s125300 |
| Pubmed ID | |
| Authors |
WG Singleton, AM Collins, AS Bienemann, CL Killick-Cole, HR Haynes, DJ Asby, CP Butts, MJ Wyatt, NU Barua, SS Gill |
| Abstract |
The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P<0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic. |
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 % |
|---|---|---|
| United Kingdom | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 73 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 1% |
| Unknown | 72 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 15 | 21% |
| Researcher | 15 | 21% |
| Student > Bachelor | 12 | 16% |
| Student > Master | 6 | 8% |
| Other | 5 | 7% |
| Other | 8 | 11% |
| Unknown | 12 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 17 | 23% |
| Engineering | 9 | 12% |
| Biochemistry, Genetics and Molecular Biology | 8 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 10% |
| Chemistry | 6 | 8% |
| Other | 13 | 18% |
| Unknown | 13 | 18% |
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 11 October 2017.
All research outputs
#16,051,091
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#1,886
of 4,122 outputs
Outputs of similar age
#243,356
of 424,972 outputs
Outputs of similar age from International Journal of Nanomedicine
#44
of 87 outputs
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