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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.

SUBMITTER: Haynes MT

PROVIDER: S-EPMC5512567 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Maximizing the Supported Bilayer Phenomenon: Liposomes Comprised Exclusively of PEGylated Phospholipids for Enhanced Systemic and Lymphatic Delivery.

Haynes Matthew T MT Huang Leaf L

ACS applied materials & interfaces 20160909 37

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 liposom ...[more]

PMID: 27580273

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Project description:Using differential scanning calorimetry and lifetime analysis of trans-parinaric acid fluorescence, we have examined how cholesterol and cholesteryl phosphocholine (CholPC) affect gel-phase properties of palmitoyl ceramide (PCer) in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dioleyol-sn-glycero-3-phosphocholine (DOPC) bilayers. By 2H NMR, we also measured fluid-phase interactions among these lipids using deuterated analogs of POPC, PCer, and cholesterol. The PCer-rich gel phase in POPC bilayers (9:1 molar ratio of POPC to PCer) was partially and similarly dissolved (and thermostability decreased) by both cholesterol and CholPC (sterol was present equimolar to PCer, or in fourfold excess). In DOPC bilayers (4:1 DOPC/PCer molar ratio), CholPC was much more efficient in dissolving the PCer-rich gel phase when compared to cholesterol. This can be interpreted as indicating that PCer interaction with POPC was stronger than PCer interaction with DOPC. PCer-CholPC interactions were also more favored in DOPC bilayers compared to POPC bilayers. In the fluid POPC-rich phase, cholesterol increased the order of the acyl chain of d2-PCer much more than did CholPC. In DOPC-rich fluid bilayers, both cholesterol and CholPC increased d2-PCer acyl chain order, and the ordering induced by CholPC was more efficient in DOPC than in POPC bilayers. In fluid POPC bilayers, the ordering of 3-d1-cholesterol by PCer was weak. In summary, we found that in the gel phase, sterol effects on the PCer-rich gel phase were markedly influenced by the acyl chain composition of the fluid PC. The same was true for fluid-phase interactions involving the sterols. Our results further suggest that PCer did not display high affinity toward either of the sterols used. We conclude that the nature of unsaturated phospholipids (POPC versus DOPC) in bilayers has major effects on the properties of ceramide gel phases and on sterol-ceramide-phospholipid interactions in such complex bilayers.

Dataset Information

Maximizing the Supported Bilayer Phenomenon: Liposomes Comprised Exclusively of PEGylated Phospholipids for Enhanced Systemic and Lymphatic Delivery.

Publications

Maximizing the Supported Bilayer Phenomenon: Liposomes Comprised Exclusively of PEGylated Phospholipids for Enhanced Systemic and Lymphatic Delivery.

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