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Lipid–PEG Conjugates Sterically Stabilize and Reduce the Toxicity of Phytantriol-Based Lyotropic Liquid Crystalline Nanoparticles

Author:
Zhai, Jiali, Hinton, Tracey M., Waddington, Lynne J., Fong, Celesta, Tran, Nhiem, Mulet, Xavier, Drummond, Calum J., Muir, Benjamin W.
Source:
Langmuir 2015 v.31 no.39 pp. 10871-10880
ISSN:
1520-5827
Subject:
composite polymers, cytotoxicity, dispersions, ethylene glycol, flocculation, hydrophilicity, hydrophobicity, liquids, medicine, moieties, molecular weight, nanoparticles, polyethylene glycol, separation, stabilizers
Abstract:
Lyotropic liquid crystalline nanoparticle dispersions are of interest as delivery vectors for biomedicine. Aqueous dispersions of liposomes, cubosomes, and hexosomes are commonly stabilized by nonionic amphiphilic block copolymers to prevent flocculation and phase separation. Pluronic stabilizers such as F127 are commonly used; however, there is increasing interest in using chemically reactive stabilizers for enhanced functionalization and specificity in therapeutic delivery applications. This study has explored the ability of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with poly(ethylene glycol) (DSPE-PEGMW) (2000 Da ≤ MW ≤ 5000 Da) to engineer and stabilize phytantriol-based lyotropic liquid crystalline dispersions. The poly(ethylene glycol) (PEG) moiety provides a tunable handle to the headgroup hydrophilicity/hydrophobicity to allow access to a range of nanoarchitectures in these systems. Specifically, it was observed that increasing PEG molecular weight promotes greater interfacial curvature of the dispersions, with liposomes (Lα) present at lower PEG molecular weight (MW 2000 Da), and a propensity for cubosomes (QIIᴾ or QIIᴰ phase) at MW 3400 Da or 5000 Da. In comparison to Pluronic F127-stabilized cubosomes, those made using DSPE-PEG₃₄₀₀ or DSPE-PEG₅₀₀₀ had enlarged internal water channels. The toxicity of these cubosomes was assessed in vitro using A549 and CHO cell lines, with cubosomes prepared using DSPE-PEG₅₀₀₀ having reduced cytotoxicity relative to their Pluronic F127-stabilized analogues.
Agid:
5773230