Surface analysis of PEGylated nano-shields on nanoparticles installed by hydrophobic anchors

TY - JOUR

T1 - Surface analysis of PEGylated nano-shields on nanoparticles installed by hydrophobic anchors

AU - Ebbesen, M F

AU - Whitehead, Bradley Joseph

AU - Gonzalez, Borja Ballarin

AU - Kingshott, P

AU - Howard, Ken

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

AB - Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

KW - nanoparticles

KW - PEG

KW - stealth

KW - surface analysis

KW - XPS

UR - http://www.scopus.com/inward/record.url?scp=84878828219&partnerID=8YFLogxK

U2 - 10.1007/s11095-013-1018-3

DO - 10.1007/s11095-013-1018-3

M3 - Journal article

C2 - 23579480

AN - SCOPUS:84878828219

SN - 0724-8741

VL - 30

SP - 1758

EP - 1767

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 7

ER -