Revealing
Dynamics of Accumulation of Systemically
Injected Liposomes in the Skin by Intravital Microscopy
Posted on 2017-10-18 - 18:23
Accumulation
of intravenously injected cytotoxic liposomes in the
skin induces serious toxicity. We used single time point and longitudinal
intravital microscopy to understand skin accumulation dynamics of
non-PEGylated and PEGylated liposomes after systemic injection into
mice. Non-PEGylated egg phosphatidylcholine (PC) liposomes showed
short circulation half-life (1.3 h) and immediate aggregation in the
blood, with some aggregates lodging in skin microvasculature soon
after the injection. At 24 h, and more prominently at 48 h postinjection,
liposomes appeared in dermal and subdermal cells. PEGylated egg PC
liposomes showed long circulation half-life (22 h) and no aggregation
in the blood. PEGylated liposomes started to accumulate in the skin
microvasculature as soon as 5 min after the injection. Within 3 h
postinjection, PEGylated liposomes accumulated in extravascular cells
in the dermis and subdermis. Liposomes were present in the skin for
at least 7 days postinjection. A regulatory approved PEGylated liposomal
doxorubicin (LipoDox) and empty liposomes of the same composition
as LipoDox showed similar skin distribution as PEGylated egg PC liposomes,
suggesting that this phenomenon is relevant to liposomes of different
lipid composition. Decorating liposomes with shorter PEGs (350 or
700) in addition to PEG 2000 did not decrease the deposition. Outside
the capillaries, liposomes partially colocalized with CD45-, F4/80+
cells. The accumulation of liposomes was not due to prior neutrophil/platelet
binding and transport across endothelium. Moreover, our studies have
excluded a role of complement in the skin accumulation of liposomes.
Further understanding of mechanisms of this important phenomenon can
improve the safety of liposomal nanocarriers.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Griffin, James
I.; Wang, Guankui; Smith, Weston J.; Vu, Vivian P.; Scheinman, Robert; Stitch, Dominik; et al. (2017). Revealing
Dynamics of Accumulation of Systemically
Injected Liposomes in the Skin by Intravital Microscopy. ACS Publications. Collection. https://doi.org/10.1021/acsnano.7b06524
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (9)
JG
James
I. Griffin
GW
Guankui Wang
WS
Weston J. Smith
VV
Vivian P. Vu
RS
Robert Scheinman
DS
Dominik Stitch
RM
Radu Moldovan
SM
Seyed Moein Moghimi
DS
Dmitri Simberg