Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs

Robert Luxenhofer, Anita Schulz, Caroline Roques, Shu Li, Tatiana K Bronich, Elena V. Batrakova, Rainer Jordan, Alexander V. Kabanov

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

Solubilization of highly hydrophobic drugs with carriers that are non-toxic, non-immunogenic and well-defined remains a major obstacle in pharmaceutical sciences. Well-defined amphiphilic di- and triblock copolymers based on poly(2-oxazolines) were prepared and used for the solubilization of Paclitaxel (PTX) and other water-insoluble drugs. Probing the polymer micelles in water with the fluorescence probe pyrene, an unusual high polar microenvironment of the probe was observed. This coincides with an extraordinary large loading capacity for PTX of 45. wt.% active drug in the formulation as well as high water solubility of the resulting formulation. Physicochemical properties of the formulations, ease of preparation and stability upon lyophilization, low toxicity and immunogenicity suggest that poly(2-oxazoline)s are promising candidates for the delivery of highly challenging drugs. Furthermore, we demonstrate that PTX is fully active and provides superior tumor inhibition as compared to the commercial micellar formulation.

Original languageEnglish (US)
Pages (from-to)4972-4979
Number of pages8
JournalBiomaterials
Volume31
Issue number18
DOIs
StatePublished - Jun 1 2010

Fingerprint

Drug Delivery Systems
Paclitaxel
Block copolymers
Water
Pharmaceutical Preparations
Drug Compounding
Drug Carriers
Freeze Drying
Pyrene
Micelles
Solubility
Drug products
Toxicity
Tumors
Polymers
Fluorescence
poly(2-oxazoline)
Neoplasms

Keywords

  • Drug delivery
  • Polymer micelles
  • Polymerization
  • Polyoxazolines
  • Solvatochromism

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Luxenhofer, R., Schulz, A., Roques, C., Li, S., Bronich, T. K., Batrakova, E. V., ... Kabanov, A. V. (2010). Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs. Biomaterials, 31(18), 4972-4979. https://doi.org/10.1016/j.biomaterials.2010.02.057

Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs. / Luxenhofer, Robert; Schulz, Anita; Roques, Caroline; Li, Shu; Bronich, Tatiana K; Batrakova, Elena V.; Jordan, Rainer; Kabanov, Alexander V.

In: Biomaterials, Vol. 31, No. 18, 01.06.2010, p. 4972-4979.

Research output: Contribution to journalArticle

Luxenhofer, R, Schulz, A, Roques, C, Li, S, Bronich, TK, Batrakova, EV, Jordan, R & Kabanov, AV 2010, 'Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs', Biomaterials, vol. 31, no. 18, pp. 4972-4979. https://doi.org/10.1016/j.biomaterials.2010.02.057
Luxenhofer, Robert ; Schulz, Anita ; Roques, Caroline ; Li, Shu ; Bronich, Tatiana K ; Batrakova, Elena V. ; Jordan, Rainer ; Kabanov, Alexander V. / Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs. In: Biomaterials. 2010 ; Vol. 31, No. 18. pp. 4972-4979.
@article{f28cb99c6a2d46648d578f3942ac0397,
title = "Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs",
abstract = "Solubilization of highly hydrophobic drugs with carriers that are non-toxic, non-immunogenic and well-defined remains a major obstacle in pharmaceutical sciences. Well-defined amphiphilic di- and triblock copolymers based on poly(2-oxazolines) were prepared and used for the solubilization of Paclitaxel (PTX) and other water-insoluble drugs. Probing the polymer micelles in water with the fluorescence probe pyrene, an unusual high polar microenvironment of the probe was observed. This coincides with an extraordinary large loading capacity for PTX of 45. wt.{\%} active drug in the formulation as well as high water solubility of the resulting formulation. Physicochemical properties of the formulations, ease of preparation and stability upon lyophilization, low toxicity and immunogenicity suggest that poly(2-oxazoline)s are promising candidates for the delivery of highly challenging drugs. Furthermore, we demonstrate that PTX is fully active and provides superior tumor inhibition as compared to the commercial micellar formulation.",
keywords = "Drug delivery, Polymer micelles, Polymerization, Polyoxazolines, Solvatochromism",
author = "Robert Luxenhofer and Anita Schulz and Caroline Roques and Shu Li and Bronich, {Tatiana K} and Batrakova, {Elena V.} and Rainer Jordan and Kabanov, {Alexander V.}",
year = "2010",
month = "6",
day = "1",
doi = "10.1016/j.biomaterials.2010.02.057",
language = "English (US)",
volume = "31",
pages = "4972--4979",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "18",

}

TY - JOUR

T1 - Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs

AU - Luxenhofer, Robert

AU - Schulz, Anita

AU - Roques, Caroline

AU - Li, Shu

AU - Bronich, Tatiana K

AU - Batrakova, Elena V.

AU - Jordan, Rainer

AU - Kabanov, Alexander V.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Solubilization of highly hydrophobic drugs with carriers that are non-toxic, non-immunogenic and well-defined remains a major obstacle in pharmaceutical sciences. Well-defined amphiphilic di- and triblock copolymers based on poly(2-oxazolines) were prepared and used for the solubilization of Paclitaxel (PTX) and other water-insoluble drugs. Probing the polymer micelles in water with the fluorescence probe pyrene, an unusual high polar microenvironment of the probe was observed. This coincides with an extraordinary large loading capacity for PTX of 45. wt.% active drug in the formulation as well as high water solubility of the resulting formulation. Physicochemical properties of the formulations, ease of preparation and stability upon lyophilization, low toxicity and immunogenicity suggest that poly(2-oxazoline)s are promising candidates for the delivery of highly challenging drugs. Furthermore, we demonstrate that PTX is fully active and provides superior tumor inhibition as compared to the commercial micellar formulation.

AB - Solubilization of highly hydrophobic drugs with carriers that are non-toxic, non-immunogenic and well-defined remains a major obstacle in pharmaceutical sciences. Well-defined amphiphilic di- and triblock copolymers based on poly(2-oxazolines) were prepared and used for the solubilization of Paclitaxel (PTX) and other water-insoluble drugs. Probing the polymer micelles in water with the fluorescence probe pyrene, an unusual high polar microenvironment of the probe was observed. This coincides with an extraordinary large loading capacity for PTX of 45. wt.% active drug in the formulation as well as high water solubility of the resulting formulation. Physicochemical properties of the formulations, ease of preparation and stability upon lyophilization, low toxicity and immunogenicity suggest that poly(2-oxazoline)s are promising candidates for the delivery of highly challenging drugs. Furthermore, we demonstrate that PTX is fully active and provides superior tumor inhibition as compared to the commercial micellar formulation.

KW - Drug delivery

KW - Polymer micelles

KW - Polymerization

KW - Polyoxazolines

KW - Solvatochromism

UR - http://www.scopus.com/inward/record.url?scp=77951978742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951978742&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2010.02.057

DO - 10.1016/j.biomaterials.2010.02.057

M3 - Article

VL - 31

SP - 4972

EP - 4979

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 18

ER -