The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs

M. Habib Ali, Behfar Moghaddam, Daniel J. Kirby, Afzal R. Mohammed, Yvonne Perrie

Research output: Contribution to journalArticle

Abstract

Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes, they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayers forming, whilst asymmetric lipids formed less condensed monolayers. However, this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency. © 2012 Elsevier B.V. All rights reserved.
LanguageEnglish
Pages225-232
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume453
Issue number1
Early online date2 Jul 2012
DOIs
Publication statusPublished - 30 Aug 2013

Fingerprint

Liposomes
Lipids
Water
Pharmaceutical Preparations
Product Packaging
Drug Delivery Systems
Solubility
Phospholipids

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Controlled Release. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Ali, MH, Moghaddam, B, Kirby, DJ, Mohammed, AR & Perrie, Y, 'The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs' International journal of pharmaceutics, vol 453, no. 1 (2012) DOI http://dx.doi.org/10.1016/j.ijpharm.2012.06.056

M. Habib Ali was funded the Engineering and Physical Sciences Research Council (Grant GR/S61287/01). Behfar Moghaddam was funded by an Aston University International Student Scholarship.

Supplementary data available on the journal website.

Keywords

  • liposomes
  • low soluble drugs
  • Bilayer drug loading
  • solubilisation
  • monolayer studies

Cite this

@article{cfc6cbfd198144ce8272114c8b0f51cb,
title = "The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs",
abstract = "Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes, they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayers forming, whilst asymmetric lipids formed less condensed monolayers. However, this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency. {\circledC} 2012 Elsevier B.V. All rights reserved.",
keywords = "liposomes, low soluble drugs, Bilayer drug loading, solubilisation, monolayer studies",
author = "Ali, {M. Habib} and Behfar Moghaddam and Kirby, {Daniel J.} and Mohammed, {Afzal R.} and Yvonne Perrie",
note = "NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Controlled Release. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Ali, MH, Moghaddam, B, Kirby, DJ, Mohammed, AR & Perrie, Y, 'The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs' International journal of pharmaceutics, vol 453, no. 1 (2012) DOI http://dx.doi.org/10.1016/j.ijpharm.2012.06.056 M. Habib Ali was funded the Engineering and Physical Sciences Research Council (Grant GR/S61287/01). Behfar Moghaddam was funded by an Aston University International Student Scholarship. Supplementary data available on the journal website.",
year = "2013",
month = "8",
day = "30",
doi = "10.1016/j.ijpharm.2012.06.056",
language = "English",
volume = "453",
pages = "225--232",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1",

}

The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs. / Ali, M. Habib; Moghaddam, Behfar; Kirby, Daniel J.; Mohammed, Afzal R.; Perrie, Yvonne.

In: International Journal of Pharmaceutics, Vol. 453, No. 1, 30.08.2013, p. 225-232.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs

AU - Ali, M. Habib

AU - Moghaddam, Behfar

AU - Kirby, Daniel J.

AU - Mohammed, Afzal R.

AU - Perrie, Yvonne

N1 - NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Controlled Release. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Ali, MH, Moghaddam, B, Kirby, DJ, Mohammed, AR & Perrie, Y, 'The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs' International journal of pharmaceutics, vol 453, no. 1 (2012) DOI http://dx.doi.org/10.1016/j.ijpharm.2012.06.056 M. Habib Ali was funded the Engineering and Physical Sciences Research Council (Grant GR/S61287/01). Behfar Moghaddam was funded by an Aston University International Student Scholarship. Supplementary data available on the journal website.

PY - 2013/8/30

Y1 - 2013/8/30

N2 - Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes, they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayers forming, whilst asymmetric lipids formed less condensed monolayers. However, this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency. © 2012 Elsevier B.V. All rights reserved.

AB - Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes, they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayers forming, whilst asymmetric lipids formed less condensed monolayers. However, this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency. © 2012 Elsevier B.V. All rights reserved.

KW - liposomes

KW - low soluble drugs

KW - Bilayer drug loading

KW - solubilisation

KW - monolayer studies

UR - http://www.scopus.com/inward/record.url?scp=84884166695&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2012.06.056

DO - 10.1016/j.ijpharm.2012.06.056

M3 - Article

VL - 453

SP - 225

EP - 232

JO - International Journal of Pharmaceutics

T2 - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1

ER -