Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics

Roxane Ridolfo, Benjamin C. Ede, Paraskevi Diamanti, Paul B. White, Adam W. Perriman, Jan C.M. van Hest, Allison Blair, David S. Williams

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

The stabilization and transport of low-solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self-assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)-block-poly(trimethylene carbonate), synthesized via organocatalyzed ring-opening polymerization, undergo assembly into highly uniform, drug-loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug-loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).

LanguageEnglish
Article number1703774
Number of pages10
JournalSmall
Volume14
Issue number12
DOIs
StatePublished - 12 Jul 2018

Fingerprint

Ethylene Glycol
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hydration
Nanomedicine
Drug Compounding
Micelles
Polymerization
Pharmaceutical Preparations
Nanoparticles
Solubility
Neoplasms
Purification
Toxicity
Technology
Copolymers
Medical nanotechnology
Therapeutics
Ring opening polymerization
Ethylene glycol
Encapsulation

Keywords

  • Acute leukemia
  • Drug delivery
  • Nanomedicine
  • Parthenolide
  • Self-assembly

Cite this

Ridolfo, R., Ede, B. C., Diamanti, P., White, P. B., Perriman, A. W., van Hest, J. C. M., ... Williams, D. S. (2018). Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics. Small, 14(12), [1703774]. DOI: 10.1002/smll.201703774
Ridolfo, Roxane ; Ede, Benjamin C. ; Diamanti, Paraskevi ; White, Paul B. ; Perriman, Adam W. ; van Hest, Jan C.M. ; Blair, Allison ; Williams, David S./ Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics. In: Small. 2018 ; Vol. 14, No. 12.
@article{af3054f47aa14ffb8ae9fef07c8c3538,
title = "Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics",
abstract = "The stabilization and transport of low-solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self-assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)-block-poly(trimethylene carbonate), synthesized via organocatalyzed ring-opening polymerization, undergo assembly into highly uniform, drug-loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug-loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).",
keywords = "Acute leukemia, Drug delivery, Nanomedicine, Parthenolide, Self-assembly",
author = "Roxane Ridolfo and Ede, {Benjamin C.} and Paraskevi Diamanti and White, {Paul B.} and Perriman, {Adam W.} and {van Hest}, {Jan C.M.} and Allison Blair and Williams, {David S.}",
year = "2018",
month = "7",
day = "12",
doi = "10.1002/smll.201703774",
language = "English",
volume = "14",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley-VCH Verlag",
number = "12",

}

Ridolfo, R, Ede, BC, Diamanti, P, White, PB, Perriman, AW, van Hest, JCM, Blair, A & Williams, DS 2018, 'Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics' Small, vol. 14, no. 12, 1703774. DOI: 10.1002/smll.201703774

Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics. / Ridolfo, Roxane; Ede, Benjamin C.; Diamanti, Paraskevi; White, Paul B.; Perriman, Adam W.; van Hest, Jan C.M.; Blair, Allison; Williams, David S.

In: Small, Vol. 14, No. 12, 1703774, 12.07.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics

AU - Ridolfo,Roxane

AU - Ede,Benjamin C.

AU - Diamanti,Paraskevi

AU - White,Paul B.

AU - Perriman,Adam W.

AU - van Hest,Jan C.M.

AU - Blair,Allison

AU - Williams,David S.

PY - 2018/7/12

Y1 - 2018/7/12

N2 - The stabilization and transport of low-solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self-assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)-block-poly(trimethylene carbonate), synthesized via organocatalyzed ring-opening polymerization, undergo assembly into highly uniform, drug-loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug-loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).

AB - The stabilization and transport of low-solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self-assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)-block-poly(trimethylene carbonate), synthesized via organocatalyzed ring-opening polymerization, undergo assembly into highly uniform, drug-loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug-loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).

KW - Acute leukemia

KW - Drug delivery

KW - Nanomedicine

KW - Parthenolide

KW - Self-assembly

UR - http://www.scopus.com/inward/record.url?scp=85050503354&partnerID=8YFLogxK

U2 - 10.1002/smll.201703774

DO - 10.1002/smll.201703774

M3 - Article

VL - 14

JO - Small

T2 - Small

JF - Small

SN - 1613-6810

IS - 12

M1 - 1703774

ER -

Ridolfo R, Ede BC, Diamanti P, White PB, Perriman AW, van Hest JCM et al. Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics. Small. 2018 Jul 12;14(12). 1703774. Available from, DOI: 10.1002/smll.201703774