TY - JOUR
T1 - A structurally diverse library of glycerol monooleate/oleic acid non-lamellar liquid crystalline nanodispersions stabilized with nonionic methoxypoly(ethylene glycol) (mPEG)-lipids showing variable complement activation properties
AU - Yu Helvig, Shen
AU - Woythe, Laura
AU - Pham, Simon
AU - Bor, Gizem
AU - Andersen, Helene
AU - Moein Moghimi, Seyed
AU - Yaghmur, Anan
PY - 2021/1/15
Y1 - 2021/1/15
N2 - Pluronic F127-stabilized non-lamellar liquid crystalline aqueous nanodispersions are promising injectable platforms for drug and contrast agent delivery. These nanodispersions, however, trigger complement activation in the human blood, where the extent of complement activation and opsonization processes may compromise their biological performance and safety. Here, we introduce a broad family of nanodispersions from glycerol monooleate (GMO) and oleic acid (OA) in different weight ratios, and stabilized with a plethora of nonionic methoxypoly(ethylene glycol) (mPEG)-lipids of different PEG chain length and variable lipid moiety (monounsaturated or saturated diglycerides or D-α-tocopheryl succinate). Through an integrated biophysical approach involving dynamic light scattering, synchrotron small-angle scattering, and cryo-transmission electron microscopy, we examine the impact of nonionic mPEG-lipid stabilization on size, internal self-assembled architecture, and gross morphological characteristics of nanodispersions. The results show how the nonionic mPEG-lipid type and concentration, and dependent on GMO/OA weight ratio, can variably modulate the internal architectures of nanoparticles. Assessment of complement profiling from selected nanodispersions with diverse structural heterogeneity further suggests a variable modulatory role for the lipid type of the nonionic mPEG-lipid in the extent of complement activation, which span from no activation to moderate to high levels. We comment on plausible mechanisms driving the observed complement activation variability and discuss the potential utility of these nanodispersions for future development of injectable nanopharmaceuticals.
AB - Pluronic F127-stabilized non-lamellar liquid crystalline aqueous nanodispersions are promising injectable platforms for drug and contrast agent delivery. These nanodispersions, however, trigger complement activation in the human blood, where the extent of complement activation and opsonization processes may compromise their biological performance and safety. Here, we introduce a broad family of nanodispersions from glycerol monooleate (GMO) and oleic acid (OA) in different weight ratios, and stabilized with a plethora of nonionic methoxypoly(ethylene glycol) (mPEG)-lipids of different PEG chain length and variable lipid moiety (monounsaturated or saturated diglycerides or D-α-tocopheryl succinate). Through an integrated biophysical approach involving dynamic light scattering, synchrotron small-angle scattering, and cryo-transmission electron microscopy, we examine the impact of nonionic mPEG-lipid stabilization on size, internal self-assembled architecture, and gross morphological characteristics of nanodispersions. The results show how the nonionic mPEG-lipid type and concentration, and dependent on GMO/OA weight ratio, can variably modulate the internal architectures of nanoparticles. Assessment of complement profiling from selected nanodispersions with diverse structural heterogeneity further suggests a variable modulatory role for the lipid type of the nonionic mPEG-lipid in the extent of complement activation, which span from no activation to moderate to high levels. We comment on plausible mechanisms driving the observed complement activation variability and discuss the potential utility of these nanodispersions for future development of injectable nanopharmaceuticals.
KW - Complement activation
KW - Cryogenic transmission electron microscopy
KW - Cubosomes
KW - D-α-tocopheryl succinate
KW - Hexosomes
KW - Micellar cubosomes
KW - mPEG-diacylglycerol
KW - synchrotron small angle X-ray scattering
UR - http://www.scopus.com/inward/record.url?scp=85090424621&partnerID=8YFLogxK
U2 - 10.1016/j.jcis.2020.08.085
DO - 10.1016/j.jcis.2020.08.085
M3 - Article
C2 - 32919118
AN - SCOPUS:85090424621
VL - 582
SP - 906
EP - 917
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
SN - 0021-9797
IS - Pt B
ER -