期刊
PHARMACEUTICAL RESEARCH
卷 30, 期 7, 页码 1758-1767出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-013-1018-3
关键词
nanoparticles; PEG; stealth; surface analysis; XPS
资金
- Lundbeck Foundation through Lundbeck Foundation Nanomedicine Center for Individualised Management of Tissue Damage and Regeneration
This work describes a method for functionalisation of nanoparticle surfaces with hydrophilic nano-shields and the application of advanced surface characterisation to determine PEG amount and accumulation at the outmost 10 nm surface that is the predominant factor in determining protein and cellular interactions. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared with a hydrophilic PEGylated nano-shield inserted at different levels by hydrophobic anchoring using either a phospholipid-PEG conjugate or the copolymer PLGA-block-PEG by an emulsification/diffusion method. Surface and bulk analysis was performed including X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy (NMR) and zeta potential. Cellular uptake was investigated in RAW 264.7 macrophages by flow cytometry. Sub-micron nanoparticles were formed and the combination of (NMR) and XPS revealed increasing PEG levels at the particle surface at higher PLGA-b-PEG copolymer levels. Reduced cellular interaction with RAW 264.7 cells was demonstrated that correlated with greater surface presentation of PEG. This work demonstrates a versatile procedure for decorating nanoparticle surfaces with hydrophilic nano-shields. XPS in combination with NMR enabled precise determination of PEG at the outmost surface to predict and optimize the biological performance of nanoparticle-based drug delivery.
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