期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 37, 页码 24361-24367出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b05534
关键词
liposome calcium phosphate; PEGylation; kinetics; distribution; tumor accumulation; lymphatic drainage
资金
- NIH [CA149387, CA198999, DK100664]
- Royster Society of Fellows at UNC
- American Foundation for Pharmaceutical Education (AFPE)
Traditional liposomes degrade into lower-order A 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 5 for the first time a liposome coated exclusively by PEGylated, phospholipids, utilizing lipid-coated calcium phosphate (CaF) cores of diverse sizes (10-15 nm, 30-40 nm) as well as varying polyethylene glycol (PEG) chain lengths (3505000 Da). Such folly-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.
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