title: Maximizing the Supported Bilayer Phenomenon: Liposomes Comprised Exclusively of PEGylated Phospholipids for Enhanced Systemic and Lymphatic Delivery.
abstract: Traditional liposomes degrade into lower-order micelles when PEGylated to even minor degrees (6-7 mol %) and therefore can offer only limited steric exclusion against opsonization during in vivo delivery. In this work, we present for the first time a liposome coated exclusively by PEGylated phospholipids, utilizing lipid-coated calcium phosphate (CaP) cores of diverse sizes (10-15 nm, 30-40 nm) as well as varying polyethylene glycol (PEG) chain lengths (350-5000 Da). Such fully-PEGylated liposome calcium phosphate (LCP) particles exhibit a PEG chain length-dependent circulation longevity and robust immune evasion, while facilitating both strong accumulation within solid tumors upon intravenous injection and a more rapid and extensive lymphatic drainage upon subcutaneous administration. Further, these fully-PEGylated liposomes remain amenable to active targeting strategies which facilitate improved degrees of focused distribution and nanoparticle uptake, represent a lipid packing density commensurate with the formation of a lipid bilayer, and avoid use of scale-limited physical resuspension methods. We expect such improved delivery properties to translate into improved therapeutic safety and efficacy for a variety of systemic and lymphatic diseases.
authors: The Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors: Matthew T
authors: MT
authors: Haynes
authors: The Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors: Leaf
authors: L
authors: Huang
mesh_terms: D000818:Animals; D005260:Female; D008051:Lipid Bilayers; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D008823:Micelles; D010743:Phospholipids; D011092:Polyethylene Glycols
keywords: PEGylation; distribution; kinetics; liposome calcium phosphate; lymphatic drainage; tumor accumulation