Functionalized triblock copolymer vectors for the treatment of acute lymphoblastic leukemia

Robert C Deller; Paraskevi Diamanti; Gabriella Morrison; James Reilly; Benjamin C Ede; Robert Richardson; Kristian Le Vay; Andrew M Collins; Allison Blair; Adam W Perriman

doi:10.1021/acs.molpharmaceut.6b01008

Functionalized triblock copolymer vectors for the treatment of acute lymphoblastic leukemia

Robert C Deller, Paraskevi Diamanti, Gabriella Morrison, James Reilly, Benjamin C Ede, Robert Richardson, Kristian Le Vay, Andrew M Collins, Allison Blair^*, Adam W Perriman

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.

Original language	English
Pages (from-to)	722-732
Number of pages	11
Journal	Molecular Pharmaceutics
Volume	14
Issue number	3
Early online date	31 Jan 2017
DOIs	https://doi.org/10.1021/acs.molpharmaceut.6b01008
Publication status	Published - 6 Mar 2017

Research Groups and Themes

BrisSynBio
Bristol BioDesign Institute

Keywords

acute lymphoblastic leukemia (ALL)
micelle
nanoparticle
parthenolide
pluronic
poloxamer
Synthetic biology

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10.1021/acs.molpharmaceut.6b01008

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via ACS at http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.6b01008. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 5.31 MB

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@article{2818420127c54580931003be71d5e22d,

title = "Functionalized triblock copolymer vectors for the treatment of acute lymphoblastic leukemia",

abstract = "The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.",

keywords = "acute lymphoblastic leukemia (ALL), micelle, nanoparticle, parthenolide, pluronic, poloxamer, Synthetic biology",

author = "Deller, {Robert C} and Paraskevi Diamanti and Gabriella Morrison and James Reilly and Ede, {Benjamin C} and Robert Richardson and {Le Vay}, Kristian and Collins, {Andrew M} and Allison Blair and Perriman, {Adam W}",

year = "2017",

month = mar,

day = "6",

doi = "10.1021/acs.molpharmaceut.6b01008",

language = "English",

volume = "14",

pages = "722--732",

journal = "Molecular Pharmaceutics",

issn = "1543-8384",

publisher = "American Chemical Society",

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TY - JOUR

T1 - Functionalized triblock copolymer vectors for the treatment of acute lymphoblastic leukemia

AU - Deller, Robert C

AU - Diamanti, Paraskevi

AU - Morrison, Gabriella

AU - Reilly, James

AU - Ede, Benjamin C

AU - Richardson, Robert

AU - Le Vay, Kristian

AU - Collins, Andrew M

AU - Blair, Allison

AU - Perriman, Adam W

PY - 2017/3/6

Y1 - 2017/3/6

N2 - The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.

AB - The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.

KW - acute lymphoblastic leukemia (ALL)

KW - micelle

KW - nanoparticle

KW - parthenolide

KW - pluronic

KW - poloxamer

KW - Synthetic biology

UR - http://www.scopus.com/inward/record.url?scp=85017589747&partnerID=8YFLogxK

U2 - 10.1021/acs.molpharmaceut.6b01008

DO - 10.1021/acs.molpharmaceut.6b01008

M3 - Article (Academic Journal)

C2 - 28139933

SN - 1543-8384

VL - 14

SP - 722

EP - 732

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 3

ER -

Functionalized triblock copolymer vectors for the treatment of acute lymphoblastic leukemia

Abstract

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Supercharged enzyme-polymer surfactant bioblocks for the preparation of organophosphate decontaminating materials

Photo-oxidation and cryofluorescence for Correlative Light Electron Microscopy

Functional Biomolecular Liquids

Wolfson Bioimaging Facility

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Functionalized triblock copolymer vectors for the treatment of acute lymphoblastic leukemia

Abstract

Research Groups and Themes

Keywords

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Other files and links

Fingerprint

Projects

Supercharged enzyme-polymer surfactant bioblocks for the preparation of organophosphate decontaminating materials

Photo-oxidation and cryofluorescence for Correlative Light Electron Microscopy

Functional Biomolecular Liquids

Equipment

Wolfson Bioimaging Facility

Cite this