Hyaluronan-modified and regular multilamellar liposomes provide sub-cellular targeting to macrophages, without eliciting a pro-inflammatory response

Yifat Glucksam-Galnoy, Tsaffrir Zor, Rimona Margalit

Research output: Contribution to journalArticlepeer-review

Abstract

Macrophages, pivotal cells in onset and progression of inflammation, can benefit from sub-cellular drug targeting to the molecular loci of drug action, whether cell membrane or cell interior. Postulating manipulation of liposome size and surface properties can provide sub-cellular targeting, we studied: thermodynamics of liposome-macrophage binding; liposome cellular localizations; liposome safety including pro-inflammatory cytokine production. We aimed at extending the body of knowledge on interactions of regular unilamellar (RL-ULV) and multilamellar (RL-MLV) liposomes with macrophages. We investigated, for the first time, the interactions of hyaluronan (HA) surface-modified liposomes (HA-ULV and HA-MLV) with macrophages, with respect to multiple equilibria binding combined with cellular localization. Macrophages bound all four liposome types, substantially-favoring the two MLV species over the two ULV species, and internalizing only RL-MLV. Three macrophage-internalization inhibitors (2-deoxyglucose, LY294002 and Wortmannin) reduced RL-MLV internalization but not binding affinity nor binding capacity. Both MLV types were not detrimental to cell proliferation, nor did they elicit TNF-α production in resting and in LPS-activated macrophages. Moreover, a 24-hour exposure of LPS-activated macrophages to HA-MLV reduced TNF-α production by 40%, indicating potential for anti-inflammatory activity. In conclusion RL-MLV and HA-MLV are the liposomes of choice for delivering anti-inflammatory drugs to the macrophage surface or its interior, according to the loci of drug action.

Original languageEnglish
Pages (from-to)388-393
Number of pages6
JournalJournal of Controlled Release
Volume160
Issue number2
DOIs
StatePublished - 10 Jun 2012

Keywords

  • Hyaluronan
  • Internalization
  • Liposomes
  • Macrophage
  • TNF-α
  • Targeting

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