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PURPOSE: To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS: PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with luciferin allowed their binding to e-selectin and activated HUVEC to be quantified in vitro and their stability, pharmacokinetics and tumor accumulation to be tested in vivo using murine models. RESULTS: PSGL1 liposomes showed 5-fold (p < 0.05) greater selectin binding than identically formulated control liposomes modified with ligand that did not contain the selectin binding domain. When added to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than control liposomes. In in vivo studies PSGL1 liposomes showed similar stability and circulation to control liposomes but demonstrated a >3-fold enhancement in the level of delivery to tumors (p < 0.05). CONCLUSIONS: The technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents.

Original publication

DOI

10.1007/s11095-012-0875-5

Type

Journal article

Journal

Pharm Res

Publication Date

02/2013

Volume

30

Pages

352 - 361

Keywords

Animals, Benzothiazoles, Drug Delivery Systems, Human Umbilical Vein Endothelial Cells, Humans, Liposomes, Membrane Glycoproteins, Mice, Neoplasms, P-Selectin, Surface Properties