title: High-throughput methods for screening liposome-macrophage cell interaction.
abstract: Carriers are often an essential element of drug delivery, bestowing attributes to their cargo such as biocompatibility, enhanced delivery, extended half-life and efficacy as well as mediating specific targeting at a tissue, cell or intracellular level. Liposomes and lipid-based carriers have been investigated for decades for this purpose, many achieving clinical approval including products such as Doxil® and Myocet™. Large-scale compound screens are routinely carried out in the field of drug discovery; however, less work has been done on harnessing high-throughput methods for carrier material screening. Screening the interaction of drug carriers and materials with cells is particularly critical for the development of emerging therapies, including biomedicines, in order to facilitate the development of safe and efficient drug products. Herein, a range of liposomes of neutral, anionic and cationic charge and others that are surface-modified with mannose residues were screened for cell interaction, toxicity and immune reactivity in THP-1-derived macrophages using a high-throughput format. Liposomes were seen to be efficacious in a concentration-dependent and, for mannosylated liposomes, mannosylated cholesterol linker length-dependent manner.
authors.affiliation: a School of Pharmacy, Royal College of Surgeons in Ireland , Dublin , Ireland.
authors.forename: Ciara
authors.initials: C
authors.lastname: Kelly
authors.affiliation: a School of Pharmacy, Royal College of Surgeons in Ireland , Dublin , Ireland.
authors.forename: Ciaran
authors.initials: C
authors.lastname: Lawlor
authors.affiliation: a School of Pharmacy, Royal College of Surgeons in Ireland , Dublin , Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Burke
authors.affiliation: b Department of Pharmaceutical and Medicinal Chemistry , Royal College of Surgeons in Ireland , Dublin , Ireland.
authors.forename: James W
authors.initials: JW
authors.lastname: Barlow
authors.affiliation: a School of Pharmacy, Royal College of Surgeons in Ireland , Dublin , Ireland.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Ramsey
authors.affiliation: c Department of Molecular and Cellular Therapeutics , Royal College of Surgeons in Ireland , Dublin , Ireland , and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jefferies
authors.affiliation: a School of Pharmacy, Royal College of Surgeons in Ireland , Dublin , Ireland.|d Trinity Centre for Bioengineering, Trinity College Dublin , Dublin , Ireland.
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Cryan
keywords: High-content analysis; high-content screening; liposomes; nanoparticles; nanotoxicology