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PEGylated Azide functionalized Liposomes Containing Drug Nanocrystals for Targeted Delivery .pdf


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Biochempeg

www.biochempeg.com

PEGylated Azide-functionalized Liposomes
Containing Drug Nanocrystals for Targeted Delivery
Liposomal formulations have important therapeutic applications in anti-cancer
treatments but current formulations suffer from serious side effects, high
dosage requirements and prolonged treatment. Research funded by Australian
Research Council (ARC) Centre of Excellence in Bio-Nano Science and
Technology (CBNS) show that 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.

PEGylated azide-functionalized liposomes were successfully prepared to

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contain ciprofloxacin drug nanocrystals as a model nanocrystallized cargo,
analogous to the elongated non-PEGylated liposomes with the same drug
nanocrystals. This is the first time that induced nanocrystallization using the
freeze-thaw process has been demonstrated for a PEGylated liposome system.
Cryo-TEM micrographs also showed that the PEGylated liposomes were
spherical in shape before drug crystallization and stretched by the drug
nanocrystal after freeze-thawing. The SANS and USANS data were consistent
with the cryo-TEM observations. X-ray scattering profiles of the liposome
samples showed diffraction of drug nanocrystals only in the freeze-thawed
samples, confirming that drug nanocrystals formed in the thawing step of the
freeze-thaw process, giving an ensemble picture of the novel drug delivery
system, complementary to the cryo-TEM micrographs. The new unidentified
ciprofloxacin polymorph formed was able to accommodate inside the
liposomes and formed elongated liposomes opening great opportunities for
using drug nanocrystals for drug delivery. Surface “click”-functionalization of
the liposomes containing the nanocrystals was also confirmed. Overall, a drug
delivery system of azide-functionalized PEGylated liposomes with
encapsulated drug nanocrystals was successfully established presenting a
new opportunity for future anti-cancer targeted delivery.


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