Microfluidic preparation of drug-loaded PEGylated liposomes, and the impact of liposome size on tumour retention and penetration

Yao Da Dong, Estefania Tchung, Cameron Nowell, Sadik Kaga, Nathania Leong, Dharmini Mehta, Lisa M. Kaminskas, Ben J. Boyd

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Understanding the effect of liposome size on tendency for accumulation in tumour tissue requires preparation of defined populations of different sized particles. However, controlling the size distributions without changing the lipid composition is difficult, and differences in compositions itself modify distribution behaviour. Here, a commercial microfluidic format as well as traditional methods was used to prepare doxorubicin-loaded liposomes of different size distributions but with the same lipid composition, and drug retention, biodistribution and localization in tumour tissues were evaluated. The small (∼50 nm diameter) liposomes prepared by microfluidics and large (∼75 nm diameter) liposomes displayed similar drug retention in in vitro release studies, and similar biodistribution patterns in tumour-bearing mice. However, the extent of extravasation was clearly dependent on size of the liposomes, with the small liposomes showing tissue distribution beyond the vascular area compared to the large liposomes. The use of microfluidics to prepare smaller size distribution liposomes compared to sonication methods is demonstrated, and allowed preparation of different size distribution drug carriers from the same lipid composition to enable new understanding of tissue distribution in compositionally consistent materials is demonstrated.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Liposome Research
DOIs
Publication statusAccepted/In press - 21 Nov 2017

Keywords

  • biodistribution
  • Liposome
  • microfluidics
  • size distribution
  • tumour penetration

Cite this

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title = "Microfluidic preparation of drug-loaded PEGylated liposomes, and the impact of liposome size on tumour retention and penetration",
abstract = "Understanding the effect of liposome size on tendency for accumulation in tumour tissue requires preparation of defined populations of different sized particles. However, controlling the size distributions without changing the lipid composition is difficult, and differences in compositions itself modify distribution behaviour. Here, a commercial microfluidic format as well as traditional methods was used to prepare doxorubicin-loaded liposomes of different size distributions but with the same lipid composition, and drug retention, biodistribution and localization in tumour tissues were evaluated. The small (∼50 nm diameter) liposomes prepared by microfluidics and large (∼75 nm diameter) liposomes displayed similar drug retention in in vitro release studies, and similar biodistribution patterns in tumour-bearing mice. However, the extent of extravasation was clearly dependent on size of the liposomes, with the small liposomes showing tissue distribution beyond the vascular area compared to the large liposomes. The use of microfluidics to prepare smaller size distribution liposomes compared to sonication methods is demonstrated, and allowed preparation of different size distribution drug carriers from the same lipid composition to enable new understanding of tissue distribution in compositionally consistent materials is demonstrated.",
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Microfluidic preparation of drug-loaded PEGylated liposomes, and the impact of liposome size on tumour retention and penetration. / Dong, Yao Da; Tchung, Estefania; Nowell, Cameron; Kaga, Sadik; Leong, Nathania; Mehta, Dharmini; Kaminskas, Lisa M.; Boyd, Ben J.

In: Journal of Liposome Research, 21.11.2017, p. 1-9.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Dong, Yao Da

AU - Tchung, Estefania

AU - Nowell, Cameron

AU - Kaga, Sadik

AU - Leong, Nathania

AU - Mehta, Dharmini

AU - Kaminskas, Lisa M.

AU - Boyd, Ben J.

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AB - Understanding the effect of liposome size on tendency for accumulation in tumour tissue requires preparation of defined populations of different sized particles. However, controlling the size distributions without changing the lipid composition is difficult, and differences in compositions itself modify distribution behaviour. Here, a commercial microfluidic format as well as traditional methods was used to prepare doxorubicin-loaded liposomes of different size distributions but with the same lipid composition, and drug retention, biodistribution and localization in tumour tissues were evaluated. The small (∼50 nm diameter) liposomes prepared by microfluidics and large (∼75 nm diameter) liposomes displayed similar drug retention in in vitro release studies, and similar biodistribution patterns in tumour-bearing mice. However, the extent of extravasation was clearly dependent on size of the liposomes, with the small liposomes showing tissue distribution beyond the vascular area compared to the large liposomes. The use of microfluidics to prepare smaller size distribution liposomes compared to sonication methods is demonstrated, and allowed preparation of different size distribution drug carriers from the same lipid composition to enable new understanding of tissue distribution in compositionally consistent materials is demonstrated.

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