| Title |
Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels – A Strategy for Brain Cancer Treatments
|
|---|---|
| Published in |
Pharmaceutical Research, February 2016
|
| DOI | 10.1007/s11095-016-1872-x |
| Pubmed ID | |
| Authors |
Funmilola A. Fisusi, Adeline Siew, Kar Wai Chooi, Omotunde Okubanjo, Natalie Garrett, Katerina Lalatsa, Dolores Serrano, Ian Summers, Julian Moger, Paul Stapleton, Ronit Satchi-Fainaro, Andreas G Schätzlein, Ijeoma F. Uchegbu |
| Abstract |
The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. Mice were dosed with either intravenous lomustine Molecular Envelope Technology (MET) nanoparticles (13 mg kg(-1)) or ethanolic lomustine (6.5 mg kg(-1)) and tissues analysed. Efficacy was assessed in an orthotopic U-87 MG glioblastoma model, following intravenous MET lomustine (daily 13 mg kg(-1)) or ethanolic lomustine (daily 1.2 mg kg(-1) - the highest repeated dose possible). Myelosuppression and MET particle macrophage uptake were also investigated. The MET formulation resulted in modest brain targeting (brain/ bone AUC0-4h ratios for MET and ethanolic lomustine = 0.90 and 0.53 respectively and brain/ liver AUC0-4h ratios for MET and ethanolic lomustine = 0.24 and 0.15 respectively). The MET formulation significantly increased mice (U-87 MG tumours) survival times; with MET lomustine, ethanolic lomustine and untreated mean survival times of 33.2, 22.5 and 21.3 days respectively and there were no material treatment-related differences in blood and femoral cell counts. Macrophage uptake is slower for MET nanoparticles than for liposomes. Particulate drug formulations improved brain tumour therapy without major bone marrow toxicity. |
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 % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 3% |
| Unknown | 68 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 20% |
| Student > Master | 9 | 13% |
| Researcher | 8 | 11% |
| Student > Doctoral Student | 4 | 6% |
| Student > Bachelor | 4 | 6% |
| Other | 13 | 19% |
| Unknown | 18 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 15 | 21% |
| Medicine and Dentistry | 10 | 14% |
| Agricultural and Biological Sciences | 4 | 6% |
| Chemistry | 4 | 6% |
| Physics and Astronomy | 4 | 6% |
| Other | 9 | 13% |
| Unknown | 24 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 20 May 2022.
All research outputs
#18,447,592
of 22,856,968 outputs
Outputs from Pharmaceutical Research
#2,479
of 2,857 outputs
Outputs of similar age
#216,901
of 298,746 outputs
Outputs of similar age from Pharmaceutical Research
#31
of 37 outputs
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