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Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity

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Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity. / Pereira, Sara; Egbu, Raphael; Jannati, Gemma; Al-Jamal, Wafa' T.

In: International Journal of Pharmaceutics, Vol. 514, No. 1, 30.11.2016, p. 150-159.

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Pereira, Sara ; Egbu, Raphael ; Jannati, Gemma ; Al-Jamal, Wafa' T. / Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity. In: International Journal of Pharmaceutics. 2016 ; Vol. 514, No. 1. pp. 150-159.

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@article{5e52ebab7af340a5afe7d8176ae814b6,
title = "Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity",
abstract = "Docetaxel (DTX)-loaded liposomes have been formulated to overcome DTX solubility issue, improve its efficacy and reduce its toxicity. This study investigated the effect of steric stabilisation, varying liposome composition, and lipid:drug molar ratio on drug loading and on the physicochemical properties of the DTX-loaded liposomes. Size exclusion chromatography (SEC) was used to remove free DTX from the liposomal formulation, and its impact on drug loading and in vitro cytotoxicity was also evaluated. Liposomes composed of fluid, unsaturated lipid (DOPC:Chol:DSPE-PEG2000) showed the highest DTX loading compared to rigid, saturated lipids (DPPC:Chol:DSPE-PEG2000 and DSPC:Chol:DSPE-PEG2000). The inclusion of PEG showed a minimum effect on DTX encapsulation. Decreasing lipid:drug molar ratio from 40:1 to 5:1 led to an improvement in the loading capacities of DOPC-based liposomes only. Up to 3.6-fold decrease in drug loading was observed after liposome purification, likely due to the loss of adsorbed and loosely entrapped DTX in the SEC column. Our in vitro toxicity results in PC3 monolayer showed that non-purified, DTX-loaded DOPC:Chol liposomes were initially (24h) more potent than the purified ones, due to the fast action of the surface- adsorbed drug. However, we hypothesize that over time (48 and 72h) the purified, DTX-loaded DOPC:Chol liposomes became more toxic due to high intracellular release of encapsulated DTX. Finally, our cytotoxicity results in PC3 spheroids showed the superior activity of DTX-loaded liposomes compared to free DTX, which could overcome the DTX poor tissue penetration, drug resistance, and improve its therapeutic efficacy following systemic administration.",
keywords = "Docetaxel, Liposome, Purification, Spheroid, Prostate cancer, PC3",
author = "Sara Pereira and Raphael Egbu and Gemma Jannati and Al-Jamal, {Wafa' T}",
note = "Crown Copyright {\circledC} 2016. Published by Elsevier B.V. All rights reserved.",
year = "2016",
month = "11",
day = "30",
doi = "10.1016/j.ijpharm.2016.06.057",
language = "English",
volume = "514",
pages = "150--159",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1",

}

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TY - JOUR

T1 - Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity

AU - Pereira, Sara

AU - Egbu, Raphael

AU - Jannati, Gemma

AU - Al-Jamal, Wafa' T

N1 - Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

PY - 2016/11/30

Y1 - 2016/11/30

N2 - Docetaxel (DTX)-loaded liposomes have been formulated to overcome DTX solubility issue, improve its efficacy and reduce its toxicity. This study investigated the effect of steric stabilisation, varying liposome composition, and lipid:drug molar ratio on drug loading and on the physicochemical properties of the DTX-loaded liposomes. Size exclusion chromatography (SEC) was used to remove free DTX from the liposomal formulation, and its impact on drug loading and in vitro cytotoxicity was also evaluated. Liposomes composed of fluid, unsaturated lipid (DOPC:Chol:DSPE-PEG2000) showed the highest DTX loading compared to rigid, saturated lipids (DPPC:Chol:DSPE-PEG2000 and DSPC:Chol:DSPE-PEG2000). The inclusion of PEG showed a minimum effect on DTX encapsulation. Decreasing lipid:drug molar ratio from 40:1 to 5:1 led to an improvement in the loading capacities of DOPC-based liposomes only. Up to 3.6-fold decrease in drug loading was observed after liposome purification, likely due to the loss of adsorbed and loosely entrapped DTX in the SEC column. Our in vitro toxicity results in PC3 monolayer showed that non-purified, DTX-loaded DOPC:Chol liposomes were initially (24h) more potent than the purified ones, due to the fast action of the surface- adsorbed drug. However, we hypothesize that over time (48 and 72h) the purified, DTX-loaded DOPC:Chol liposomes became more toxic due to high intracellular release of encapsulated DTX. Finally, our cytotoxicity results in PC3 spheroids showed the superior activity of DTX-loaded liposomes compared to free DTX, which could overcome the DTX poor tissue penetration, drug resistance, and improve its therapeutic efficacy following systemic administration.

AB - Docetaxel (DTX)-loaded liposomes have been formulated to overcome DTX solubility issue, improve its efficacy and reduce its toxicity. This study investigated the effect of steric stabilisation, varying liposome composition, and lipid:drug molar ratio on drug loading and on the physicochemical properties of the DTX-loaded liposomes. Size exclusion chromatography (SEC) was used to remove free DTX from the liposomal formulation, and its impact on drug loading and in vitro cytotoxicity was also evaluated. Liposomes composed of fluid, unsaturated lipid (DOPC:Chol:DSPE-PEG2000) showed the highest DTX loading compared to rigid, saturated lipids (DPPC:Chol:DSPE-PEG2000 and DSPC:Chol:DSPE-PEG2000). The inclusion of PEG showed a minimum effect on DTX encapsulation. Decreasing lipid:drug molar ratio from 40:1 to 5:1 led to an improvement in the loading capacities of DOPC-based liposomes only. Up to 3.6-fold decrease in drug loading was observed after liposome purification, likely due to the loss of adsorbed and loosely entrapped DTX in the SEC column. Our in vitro toxicity results in PC3 monolayer showed that non-purified, DTX-loaded DOPC:Chol liposomes were initially (24h) more potent than the purified ones, due to the fast action of the surface- adsorbed drug. However, we hypothesize that over time (48 and 72h) the purified, DTX-loaded DOPC:Chol liposomes became more toxic due to high intracellular release of encapsulated DTX. Finally, our cytotoxicity results in PC3 spheroids showed the superior activity of DTX-loaded liposomes compared to free DTX, which could overcome the DTX poor tissue penetration, drug resistance, and improve its therapeutic efficacy following systemic administration.

KW - Docetaxel

KW - Liposome

KW - Purification

KW - Spheroid

KW - Prostate cancer

KW - PC3

U2 - 10.1016/j.ijpharm.2016.06.057

DO - 10.1016/j.ijpharm.2016.06.057

M3 - Article

VL - 514

SP - 150

EP - 159

JO - International Journal of Pharmaceutics

T2 - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1

ER -

ID: 97835542