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Optimized thermosensitive liposomes for selective doxorubicin delivery: Formulation development, quality analysis and bioactivity proof

In our study we examined thermosensitive liposomal formulations (TL) from the perspective to minimize the general toxicity drawbacks of chemotherapy. The TL become active in response to local hyperthermia (LH), and remain inactive at physiological conditions. Here, we formulated novel doxorubicin lo... Full description

Journal Title: Colloids and Surfaces B: Biointerfaces 01 September 2014, Vol.121, pp.248-256
Main Author: Levacheva, I
Other Authors: Samsonova, O , Tazina, E , Beck-Broichsitter, M , Levachev, S , Strehlow, B , Baryshnikova, M , Oborotova, N , Baryshnikov, A , Bakowsky, U
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0927-7765 ; E-ISSN: 1873-4367 ; DOI: 10.1016/j.colsurfb.2014.02.028
Link: https://www.sciencedirect.com/science/article/pii/S0927776514000952
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recordid: elsevier_sdoi_10_1016_j_colsurfb_2014_02_028
title: Optimized thermosensitive liposomes for selective doxorubicin delivery: Formulation development, quality analysis and bioactivity proof
format: Article
creator:
  • Levacheva, I
  • Samsonova, O
  • Tazina, E
  • Beck-Broichsitter, M
  • Levachev, S
  • Strehlow, B
  • Baryshnikova, M
  • Oborotova, N
  • Baryshnikov, A
  • Bakowsky, U
subjects:
  • Thermosensitive Liposomes
  • Stability
  • Antitumor Therapy
  • Doxorubicin
  • Engineering
  • Chemistry
  • Anatomy & Physiology
ispartof: Colloids and Surfaces B: Biointerfaces, 01 September 2014, Vol.121, pp.248-256
description: In our study we examined thermosensitive liposomal formulations (TL) from the perspective to minimize the general toxicity drawbacks of chemotherapy. The TL become active in response to local hyperthermia (LH), and remain inactive at physiological conditions. Here, we formulated novel doxorubicin loaded thermoliposomes (Dox-TL) with optimized characteristics and tested their biological activity . The liposomal membrane composition of Dox-TL and their preparation technology were adjusted for high drug loading and extended formulation stability. The 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC):1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC):cholesterol(Chol):1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (ammonium salt) (DSPE-PEG-2000) in molar ratio 9:1:0.2:0.02:0.2 and drug/lipid weight ratio 0.13–0.20/1 composition has demonstrated best results. The freshly-prepared vesicles contained 94% doxorubicin. The Dox-TL, freeze-dried with 4% sucrose, maintained high level of encapsulated drug, remained stable in serum and prevented premature drug leakage. The Dox-TL proved to be significantly less toxic at 37 °C than free Dox. In combination with local hyperthermia of 42.5 °C Dox-TL were as effective as free Dox in cell survival, and even outperformed free Dox in proliferation activity suppression, colony proliferation rate, and cellular uptake. These findings represent a solid basis for a safer and more effective antitumor therapy.
language: eng
source:
identifier: ISSN: 0927-7765 ; E-ISSN: 1873-4367 ; DOI: 10.1016/j.colsurfb.2014.02.028
fulltext: fulltext
issn:
  • 0927-7765
  • 09277765
  • 1873-4367
  • 18734367
url: Link


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titleOptimized thermosensitive liposomes for selective doxorubicin delivery: Formulation development, quality analysis and bioactivity proof
creatorLevacheva, I ; Samsonova, O ; Tazina, E ; Beck-Broichsitter, M ; Levachev, S ; Strehlow, B ; Baryshnikova, M ; Oborotova, N ; Baryshnikov, A ; Bakowsky, U
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subjectThermosensitive Liposomes ; Stability ; Antitumor Therapy ; Doxorubicin ; Engineering ; Chemistry ; Anatomy & Physiology
descriptionIn our study we examined thermosensitive liposomal formulations (TL) from the perspective to minimize the general toxicity drawbacks of chemotherapy. The TL become active in response to local hyperthermia (LH), and remain inactive at physiological conditions. Here, we formulated novel doxorubicin loaded thermoliposomes (Dox-TL) with optimized characteristics and tested their biological activity . The liposomal membrane composition of Dox-TL and their preparation technology were adjusted for high drug loading and extended formulation stability. The 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC):1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC):cholesterol(Chol):1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (ammonium salt) (DSPE-PEG-2000) in molar ratio 9:1:0.2:0.02:0.2 and drug/lipid weight ratio 0.13–0.20/1 composition has demonstrated best results. The freshly-prepared vesicles contained 94% doxorubicin. The Dox-TL, freeze-dried with 4% sucrose, maintained high level of encapsulated drug, remained stable in serum and prevented premature drug leakage. The Dox-TL proved to be significantly less toxic at 37 °C than free Dox. In combination with local hyperthermia of 42.5 °C Dox-TL were as effective as free Dox in cell survival, and even outperformed free Dox in proliferation activity suppression, colony proliferation rate, and cellular uptake. These findings represent a solid basis for a safer and more effective antitumor therapy.
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