PEGylation and surface functionalization of liposomes containing drug nanocrystals for cell-targeted delivery

Yunxin Xiao; Qingtao Liu; Andrew J. Clulow; Tang Li; Madhura Manohar; Elliot P. Gilbert; Liliana de Campo; Adrian Hawley; B. J. Boyd

doi:10.1016/j.colsurfb.2019.110362

PEGylation and surface functionalization of liposomes containing drug nanocrystals for cell-targeted delivery

Yunxin Xiao, Qingtao Liu, Andrew J. Clulow, Tang Li, Madhura Manohar, Elliot P. Gilbert, Liliana de Campo, Adrian Hawley, B. J. Boyd

Drug Delivery Disposition & Dynamics

Research output: Contribution to journal › Article › Research › peer-review

6 Citations (Scopus)

Abstract

Liposomal formulations have important therapeutic applications in anti-cancer treatments but current formulations suffer from serious side effects, high dosage requirements and prolonged treatment. In this study, PEGylated azide-functionalized liposomes containing drug nanocrystals were investigated with the aim of increasing the drug payload and achieving functionalization for targeted delivery. Liposomes were characterized using cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small and ultra-small angle neutron scattering (SANS/USANS) and small and wide angle X-ray scattering (SAXS/WAXS). Cryo-TEM experiments revealed the dimensions of the nanocrystal-loaded liposomes and the change of shape from spherical to elongated after the formation of nanocrystals. Results from SANS/USANS experiments confirmed the asymmetric particle shape. SAXS/WAXS experiments confirmed that the crystalline drug only occurred in freeze-thawed samples and correlated with a new unidentified polymorphic form of ciprofloxacin. Using a small molecule dye, dibenzocyclooctyne (DBCO)-cy5, specific conjugation between DBCO groups and surface azide groups on the liposomes was confirmed; this indicates the promise of this system for tumour-targeted delivery.

Original language	English
Article number	110362
Number of pages	10
Journal	Colloids and Surfaces B: Biointerfaces
Volume	182
DOIs	https://doi.org/10.1016/j.colsurfb.2019.110362
Publication status	Published - 1 Oct 2019

Keywords

Click chemistry
Drug nanocrystals
Liposomes
PEGylation
Scattering
Targeted delivery

Access to Document

10.1016/j.colsurfb.2019.110362

280990590-oaSubmitted manuscript, 1.21 MBLicence: Unspecified

Link to publication in Scopus

Australian Synchrotron
Office of the Vice-Provost (Research and Research Infrastructure)
Facility/equipment: Facility
Ramaciotti Centre for Cryo-Electron Microscopy
Georg Ramm (Manager), Viola M.J. Oorschot (Operator), Simon Andrew Crawford (Operator), Hariprasad Venugopal (Operator), Joan Marea Clark (Operator) & Gediminas Gervinskas (Operator)
Office of the Vice-Provost (Research and Research Infrastructure)
Facility/equipment: Facility

Cite this

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title = "PEGylation and surface functionalization of liposomes containing drug nanocrystals for cell-targeted delivery",

abstract = "Liposomal formulations have important therapeutic applications in anti-cancer treatments but current formulations suffer from serious side effects, high dosage requirements and prolonged treatment. In this study, PEGylated azide-functionalized liposomes containing drug nanocrystals were investigated with the aim of increasing the drug payload and achieving functionalization for targeted delivery. Liposomes were characterized using cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small and ultra-small angle neutron scattering (SANS/USANS) and small and wide angle X-ray scattering (SAXS/WAXS). Cryo-TEM experiments revealed the dimensions of the nanocrystal-loaded liposomes and the change of shape from spherical to elongated after the formation of nanocrystals. Results from SANS/USANS experiments confirmed the asymmetric particle shape. SAXS/WAXS experiments confirmed that the crystalline drug only occurred in freeze-thawed samples and correlated with a new unidentified polymorphic form of ciprofloxacin. Using a small molecule dye, dibenzocyclooctyne (DBCO)-cy5, specific conjugation between DBCO groups and surface azide groups on the liposomes was confirmed; this indicates the promise of this system for tumour-targeted delivery.",

keywords = "Click chemistry, Drug nanocrystals, Liposomes, PEGylation, Scattering, Targeted delivery",

author = "Yunxin Xiao and Qingtao Liu and Clulow, {Andrew J.} and Tang Li and Madhura Manohar and Gilbert, {Elliot P.} and {de Campo}, Liliana and Adrian Hawley and Boyd, {B. J.}",

year = "2019",

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doi = "10.1016/j.colsurfb.2019.110362",

language = "English",

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PEGylation and surface functionalization of liposomes containing drug nanocrystals for cell-targeted delivery. / Xiao, Yunxin; Liu, Qingtao; Clulow, Andrew J.; Li, Tang; Manohar, Madhura; Gilbert, Elliot P.; de Campo, Liliana; Hawley, Adrian; Boyd, B. J.

In: Colloids and Surfaces B: Biointerfaces, Vol. 182, 110362, 01.10.2019.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - PEGylation and surface functionalization of liposomes containing drug nanocrystals for cell-targeted delivery

AU - Xiao, Yunxin

AU - Liu, Qingtao

AU - Clulow, Andrew J.

AU - Li, Tang

AU - Manohar, Madhura

AU - Gilbert, Elliot P.

AU - de Campo, Liliana

AU - Hawley, Adrian

AU - Boyd, B. J.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Liposomal formulations have important therapeutic applications in anti-cancer treatments but current formulations suffer from serious side effects, high dosage requirements and prolonged treatment. In this study, PEGylated azide-functionalized liposomes containing drug nanocrystals were investigated with the aim of increasing the drug payload and achieving functionalization for targeted delivery. Liposomes were characterized using cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small and ultra-small angle neutron scattering (SANS/USANS) and small and wide angle X-ray scattering (SAXS/WAXS). Cryo-TEM experiments revealed the dimensions of the nanocrystal-loaded liposomes and the change of shape from spherical to elongated after the formation of nanocrystals. Results from SANS/USANS experiments confirmed the asymmetric particle shape. SAXS/WAXS experiments confirmed that the crystalline drug only occurred in freeze-thawed samples and correlated with a new unidentified polymorphic form of ciprofloxacin. Using a small molecule dye, dibenzocyclooctyne (DBCO)-cy5, specific conjugation between DBCO groups and surface azide groups on the liposomes was confirmed; this indicates the promise of this system for tumour-targeted delivery.

AB - Liposomal formulations have important therapeutic applications in anti-cancer treatments but current formulations suffer from serious side effects, high dosage requirements and prolonged treatment. In this study, PEGylated azide-functionalized liposomes containing drug nanocrystals were investigated with the aim of increasing the drug payload and achieving functionalization for targeted delivery. Liposomes were characterized using cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small and ultra-small angle neutron scattering (SANS/USANS) and small and wide angle X-ray scattering (SAXS/WAXS). Cryo-TEM experiments revealed the dimensions of the nanocrystal-loaded liposomes and the change of shape from spherical to elongated after the formation of nanocrystals. Results from SANS/USANS experiments confirmed the asymmetric particle shape. SAXS/WAXS experiments confirmed that the crystalline drug only occurred in freeze-thawed samples and correlated with a new unidentified polymorphic form of ciprofloxacin. Using a small molecule dye, dibenzocyclooctyne (DBCO)-cy5, specific conjugation between DBCO groups and surface azide groups on the liposomes was confirmed; this indicates the promise of this system for tumour-targeted delivery.

KW - Click chemistry

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KW - Liposomes

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KW - Scattering

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PEGylation and surface functionalization of liposomes containing drug nanocrystals for cell-targeted delivery

Abstract

Keywords

Access to Document

Equipment

Australian Synchrotron

Ramaciotti Centre for Cryo-Electron Microscopy

Cite this