title: Lipid-PEG conjugates sterically stabilize and reduce the toxicity of phytantriol-based lyotropic liquid crystalline nanoparticles.
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 (QII(P) or QII(D) 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.
authors.affiliation: CSIRO Manufacturing Flagship, Private Bag 10, Clayton, VIC 3169, Australia.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhai
authors.affiliation: CSIRO Biosecurity Flagship, Australian Animal Health Laboratory, 5 Portarlington Road, East Geelong, VIC 3219, Australia.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Hinton
authors.affiliation: CSIRO Manufacturing Flagship, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Waddington
authors.affiliation: CSIRO Manufacturing Flagship, Private Bag 10, Clayton, VIC 3169, Australia.|School of Applied Sciences, College of Science, Engineering and Health, RMIT University , GPO Box 2476, Melbourne, VIC 3001, Australia.
authors.forename: Celesta
authors.initials: C
authors.lastname: Fong
authors.affiliation: CSIRO Manufacturing Flagship, Private Bag 10, Clayton, VIC 3169, Australia.
authors.forename: Nhiem
authors.initials: N
authors.lastname: Tran
authors.affiliation: CSIRO Manufacturing Flagship, Private Bag 10, Clayton, VIC 3169, Australia.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mulet
authors.affiliation: School of Applied Sciences, College of Science, Engineering and Health, RMIT University , GPO Box 2476, Melbourne, VIC 3001, Australia.
authors.forename: Calum J
authors.initials: CJ
authors.lastname: Drummond
authors.affiliation: CSIRO Manufacturing Flagship, Private Bag 10, Clayton, VIC 3169, Australia.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Muir
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D005233:Fatty Alcohols / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D050866:Liquid Crystals / Q000737:chemistry* / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D003470:Culture Media; D005233:Fatty Alcohols; D008055:Lipids; D011092:Polyethylene Glycols; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol