Engineering lipid vesicles of enhanced intratumoral transport capabilities: Correlating liposome characteristics with penetration into human prostate tumor spheroids

Kostas Kostarelos, Dimitris Emfietzoglou, Alexandros Papakostas, Wei Hong Yang, Åse M. Ballangrud, George Sgouros

Research output: Contribution to journalArticlepeer-review

Abstract

Liposomes have been widely used delivery systems, particularly relevant to the development of cancer therapeutics. Numerous liposome-based drugs are in the clinic or in clinical trials today against multiple tumor types; however, systematic studies of liposome interactions with solid or metastatic tumor nodules are scarce. This study is describing the in vitro interaction between liposomes and avascular human prostate (LNCaP-LN3) tumor spheroids. The ability offluorescently labelled liposomal delivery systems of varying physicochemical characteristics to penetrate within multicellular tumor spheroids has been investigated by confocal laser scanning microscopy. A variety of liposome characteristics and experimental parameters were investigated, including lipid bilayer composition, duration of liposome-spheroid interaction, mean liposome size, steric stabilization of liposomes. Electrostatic binding between cationic liposomes and spheroids was very efficient; however, it impeded any significant penetration of the vesicles within deeper layers of the tumor spheroid. Small unilamellar liposomes of neutral surface character did not bind as efficiently but exhibited enhanced penetrative transport capabilities closer to the tumor core. Polymer-coated (sterically stabilised) liposomes exhibited almost no interaction with the spheroid, indicating that their limited diffusion within avascular tissues may be a limiting step for their use against micrometastases. Multicellular tumor spheroids were used as models of solid tumor interstitium relevant to delivery systems able to extravasate from the microcapillaries or as models of prevascularized micrometastases. This study illustrates that interactions between liposomes and other drug delivery systems with mullicellular tumor spheroids can offer critically important information with respect to optimizing solid or micrometaslalic tumor delivery and targeting strategies.

Original languageEnglish (US)
Pages (from-to)15-27
Number of pages13
JournalJournal of Liposome Research
Volume15
Issue number1-2
DOIs
StatePublished - 2005

Keywords

  • Diffusion
  • Drug delivery
  • Intratumoral transport
  • Liposome
  • Prostate
  • Tumor spheroids

ASJC Scopus subject areas

  • Pharmaceutical Science

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