Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes

Negar Sadeghi, Roel Deckers, Burcin Ozbakir, Sohail Akthar, Robbert Jan Kok, Twan Lammers, Gert Storm (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Fast hyperthermia (i.e. 39-42 °C) triggered doxorubicin release from lysolipid-containing thermosensitive liposomes (LTSL) in the tumor vasculature has been demonstrated to result in considerable enhancement of bioavailable drug levels in heated tumor tissue in preclinical tumor models. However, there is also significant leakage of doxorubicin already at 37 °C in the bloodstream, making these LTSL less efficient and increasing the risk for systemic toxicity. In conventional liposomes, cholesterol is incorporated in the bilayer to increase the stability of the liposomes. Here, we investigate the effect of cholesterol inclusion on the doxorubicin release characteristics of LTSL at 37 °C and hyperthermic temperatures.For this purpose, three LTSL formulations with 0, 5 and 10 mol% cholesterol were prepared. Inclusion of cholesterol reduced the undesired doxorubicin leakage at 37 °C in Hepes-buffered saline (HBS) as well as in fetal bovine serum (FBS). The incorporation of cholesterol in the LTSL bilayers did not influence the hyperthermia-triggered release property of the LTSL. These results were supported by DSC measurements.Therefore, in conclusion, our data indicate that cholesterol inclusion in LTSL offers a simple solution to the problem of significant leakage of doxorubicin from LTSL already at 37 °C in the bloodstream.

Original languageEnglish
Pages (from-to)778-782
Number of pages5
JournalInternational journal of pharmaceutics
Volume548
Issue number2
DOIs
Publication statusPublished - 15 Sep 2018

Fingerprint

Liposomes
Doxorubicin
Cholesterol
Fever
Neoplasms
Temperature
Serum

Keywords

  • UT-Hybrid-D
  • Doxorubicin
  • Hyperthermia
  • Local drug delivery
  • Temperature-sensitive liposomes
  • Cholesterol

Cite this

Sadeghi, Negar ; Deckers, Roel ; Ozbakir, Burcin ; Akthar, Sohail ; Kok, Robbert Jan ; Lammers, Twan ; Storm, Gert. / Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes. In: International journal of pharmaceutics. 2018 ; Vol. 548, No. 2. pp. 778-782.
@article{44707fe300d5481f8b319e07cf160c83,
title = "Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes",
abstract = "Fast hyperthermia (i.e. 39-42 °C) triggered doxorubicin release from lysolipid-containing thermosensitive liposomes (LTSL) in the tumor vasculature has been demonstrated to result in considerable enhancement of bioavailable drug levels in heated tumor tissue in preclinical tumor models. However, there is also significant leakage of doxorubicin already at 37 °C in the bloodstream, making these LTSL less efficient and increasing the risk for systemic toxicity. In conventional liposomes, cholesterol is incorporated in the bilayer to increase the stability of the liposomes. Here, we investigate the effect of cholesterol inclusion on the doxorubicin release characteristics of LTSL at 37 °C and hyperthermic temperatures.For this purpose, three LTSL formulations with 0, 5 and 10 mol{\%} cholesterol were prepared. Inclusion of cholesterol reduced the undesired doxorubicin leakage at 37 °C in Hepes-buffered saline (HBS) as well as in fetal bovine serum (FBS). The incorporation of cholesterol in the LTSL bilayers did not influence the hyperthermia-triggered release property of the LTSL. These results were supported by DSC measurements.Therefore, in conclusion, our data indicate that cholesterol inclusion in LTSL offers a simple solution to the problem of significant leakage of doxorubicin from LTSL already at 37 °C in the bloodstream.",
keywords = "UT-Hybrid-D, Doxorubicin, Hyperthermia, Local drug delivery, Temperature-sensitive liposomes, Cholesterol",
author = "Negar Sadeghi and Roel Deckers and Burcin Ozbakir and Sohail Akthar and Kok, {Robbert Jan} and Twan Lammers and Gert Storm",
note = "Elsevier deal",
year = "2018",
month = "9",
day = "15",
doi = "10.1016/j.ijpharm.2017.11.002",
language = "English",
volume = "548",
pages = "778--782",
journal = "International journal of pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "2",

}

Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes. / Sadeghi, Negar; Deckers, Roel; Ozbakir, Burcin; Akthar, Sohail; Kok, Robbert Jan; Lammers, Twan; Storm, Gert (Corresponding Author).

In: International journal of pharmaceutics, Vol. 548, No. 2, 15.09.2018, p. 778-782.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes

AU - Sadeghi, Negar

AU - Deckers, Roel

AU - Ozbakir, Burcin

AU - Akthar, Sohail

AU - Kok, Robbert Jan

AU - Lammers, Twan

AU - Storm, Gert

N1 - Elsevier deal

PY - 2018/9/15

Y1 - 2018/9/15

N2 - Fast hyperthermia (i.e. 39-42 °C) triggered doxorubicin release from lysolipid-containing thermosensitive liposomes (LTSL) in the tumor vasculature has been demonstrated to result in considerable enhancement of bioavailable drug levels in heated tumor tissue in preclinical tumor models. However, there is also significant leakage of doxorubicin already at 37 °C in the bloodstream, making these LTSL less efficient and increasing the risk for systemic toxicity. In conventional liposomes, cholesterol is incorporated in the bilayer to increase the stability of the liposomes. Here, we investigate the effect of cholesterol inclusion on the doxorubicin release characteristics of LTSL at 37 °C and hyperthermic temperatures.For this purpose, three LTSL formulations with 0, 5 and 10 mol% cholesterol were prepared. Inclusion of cholesterol reduced the undesired doxorubicin leakage at 37 °C in Hepes-buffered saline (HBS) as well as in fetal bovine serum (FBS). The incorporation of cholesterol in the LTSL bilayers did not influence the hyperthermia-triggered release property of the LTSL. These results were supported by DSC measurements.Therefore, in conclusion, our data indicate that cholesterol inclusion in LTSL offers a simple solution to the problem of significant leakage of doxorubicin from LTSL already at 37 °C in the bloodstream.

AB - Fast hyperthermia (i.e. 39-42 °C) triggered doxorubicin release from lysolipid-containing thermosensitive liposomes (LTSL) in the tumor vasculature has been demonstrated to result in considerable enhancement of bioavailable drug levels in heated tumor tissue in preclinical tumor models. However, there is also significant leakage of doxorubicin already at 37 °C in the bloodstream, making these LTSL less efficient and increasing the risk for systemic toxicity. In conventional liposomes, cholesterol is incorporated in the bilayer to increase the stability of the liposomes. Here, we investigate the effect of cholesterol inclusion on the doxorubicin release characteristics of LTSL at 37 °C and hyperthermic temperatures.For this purpose, three LTSL formulations with 0, 5 and 10 mol% cholesterol were prepared. Inclusion of cholesterol reduced the undesired doxorubicin leakage at 37 °C in Hepes-buffered saline (HBS) as well as in fetal bovine serum (FBS). The incorporation of cholesterol in the LTSL bilayers did not influence the hyperthermia-triggered release property of the LTSL. These results were supported by DSC measurements.Therefore, in conclusion, our data indicate that cholesterol inclusion in LTSL offers a simple solution to the problem of significant leakage of doxorubicin from LTSL already at 37 °C in the bloodstream.

KW - UT-Hybrid-D

KW - Doxorubicin

KW - Hyperthermia

KW - Local drug delivery

KW - Temperature-sensitive liposomes

KW - Cholesterol

UR - http://www.scopus.com/inward/record.url?scp=85035024961&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2017.11.002

DO - 10.1016/j.ijpharm.2017.11.002

M3 - Article

VL - 548

SP - 778

EP - 782

JO - International journal of pharmaceutics

JF - International journal of pharmaceutics

SN - 0378-5173

IS - 2

ER -