Presidential Greeting - American Society for Laser Medicine and ...

are still needed to prove and compare their short-term and longterm
effects.
Study: Seven healthy Chinese women received one pass of
UPCO2 treatment on left back and SPCO2 treatment on right
back. The pulse energies were 15 mJ at a density of 5%. The
clinical outcomes and side effects were evaluated by two blinded
certified dermatologists. Dermatoscope, in vivo reflectance
confocal microscopy (RCM) and high frequency ultrasonic
equipment were used to observe skin responses non-invasively.
Biopsies were taken for hematoxylin–eosin (HE) stains and
Verhoeff-iron-hematoxylin stain.
Results: RCM and the histopathology showed that SPCO 2
treatment could penetrate as deep as UPCO 2 does. Both UPCO 2
and SPCO2 treatment need about 7 days for the microscopic
epidermal necrotic debris (MEND) to shed off. The two modes
have similar efficacy in stimulating the synthesis and remodeling
of collagen and elastin, which was also confirmed by
ultrasonography image.
Conclusion: There is no significant difference between UPCO2
and SPCO 2 treatment in skin rejuvenation by histological
findings, RCM and ultrasonography observation.
#39
American Society for Laser Medicine and Surgery Abstracts 13
TRANEXAMIC ACID-CONTAINING LIPOSOMES
FOR ANTIFIBRINOLYTIC SITE-SPECIFIC
PHARMACO-LASER THERAPY OF PORT WINE
STAINS
Michal Heger, Anton I.P.M. de Kroon
Academic Medical Center, University of Amsterdam, Amsterdam,
The Netherlands; University of Utrecht, Utrecht, The Netherlands
Background: Site-specific pharmaco-laser therapy (SSPLT) is a
development stage treatment modality for refractory port wine
stains (PWS), whereby conventional selective photothermolysis is
combined with the prior administration of a prothrombotic/
antifibrinolytic-containing liposomal drug delivery system (DDS).
The aim of this study was to determine release profiles of
tranexamic acid (TA, antifibrinolytic agent) from thermosensitive
liposomes in buffer and plasma at different temperatures and
osmotic gradients and to determine liposome stability in plasma.
Study: Thermosensitive liposomes were prepared from DPPC/
DSPE-polyethylene glycol (PEG) lipids (96:4 molar ratio) and
DPPC/MPPC/DSPE-PEG (86:10:4) by the lipid film hydration
technique using 318 mM TA in 10 mM HEPES, 0.88% NaCl,
pH ¼ 7.4, 0.292 osmol/kg or with 52.8 mM calcein (self-quenching
concentration) in hypo- or iso-osmolar HEPES buffer. An offline
quantification assay was developed to determine TA release from
liposomes in buffer at the phase transition temperature (Tm) of the
bilayer and at 48C/ þ 48C/658C/908C as a function of heating
time. An online spectrofluorometric assay was employed to
determine passive leakage of calcein from the liposomes at
increasing plasma concentrations at 378C. Lastly, an RT-PCR
instrument was used to establish (online) temperature-dependent
calcein release profiles from the liposomal formulations at
increasing plasma concentrations.
Results: TA release rates from DPPC/DSPE-PEG liposomes were
13%/5.0 min, 96%/2.5 min, 107%/1.5 min, 107%/0.5 min, and 98%/
0.5 min for 39.38C/43.38C/47.38C/65.08C/90.08C, respectively. TA
release rates from DPPC/MPPC/DSPE-PEG liposomes were 0%/
5.0 min, 94%/2.0 min, 96%/1.0 min, 105%/0.5 min, and 89%/
0.5 min for 36.08C/40.08C/44.08C/65.08C/90.08C, respectively.
Passive leakage of calcein at 378C was 4.77 and 5.95%/min for
DPPC/DSPE-PEG and DPPC/MPPC/DSPE-PEG liposomes,
respectively. Osmolarity had no influence on passive leakage and
plasma reduced passive leakage rates. Plasma had no notable
impact on calcein release profiles compared to TA release profiles
in buffer at any of the assayed temperatures.
Conclusion: Both liposomal formulations are suitable for
antifibrinolytic SSPLT in that almost all TA is released within
2.5 min and no detrimental effects of plasma were found on release
kinetics and stability.
#40
TOWARDS ENHANCEMENT OF PDT EFFICACY IN
EXTRAHEPATIC CHOLANGIOCARCINOMAS
USING LIPOSOMAL PHOTOSENSITIZATION
Mans Broekgaarden, Anton, I.P.M. de Kroon,
J. Antoinette Killian, Thomas, M. van Gulik,
Michal Heger
Academic Medical Center, Amsterdam, The Netherlands,
University of Amsterdam and Biochemistry of Membranes,
Membrane Enzymology, Institute of Biomembranes,
University of Utrecht, Utrecht, The Netherlands
Background: Photodynamic therapy (PDT) yields suboptimal
results in the treatment of extrahepatic cholangiocarcinomas
(EHCCs) due to the use of inferior photosensitizers, insufficient
photosensitization of the tumor, and the biological properties of
the malignancy. To optimize PDT for these tumors, a secondgeneration
photosensitizer, zinc phthalocyanine (ZnPC), will be
encapsulated in liposomes and targeted to the tumor endothelium,
tumor cells, and interstitial spaces. Inasmuch as an appropriate
animal model is lacking, a chicken chorioallantoic membrane
(CAM) model for EHCC and other tumors was developed for
testing the PDT efficacy of the liposomal formulations. This work
describes the development of the animal model and ZnPC
liposomes for interstitial targeting.
Study: The CAM model was used to grow Sk-Cha1, HepG2, and
IGROV-1 cells into EHCCs, hepatocellular carcinomas, and
ovarian carcinomas, respectively. Tumors were imaged after 4
days of incubation using stereomicroscopy and 1,300-nm sweptsource
optical coherence tomography. Liposomes for stromal
targeting composed of 4.8 mM DPPC and 0.2 mM DSPE-PEG2000 and 0–50 mM ZnPC were characterized for size/polydispersity,
drug-to-lipid ratio, fluorescence emission, and singlet oxygen
radical-mediated membrane damage. The latter was assayed by
fluorometric calcein leakage assays from vesicles with a target
cell-like lipid composition, on which PDT was performed.
Results: Successful tumor growth of Sk-Cha1, HepG2, and
IGROV-1 cells was achieved in ovo, although tumor-type
associated differences in vascularization and growing patterns
were observed. Liposomes with various concentrations ZnPC had
an average size of 105.4 6.4 nm with a polydispersity of
0.37 0.12. Optimal ZnPC fluorescence was observed at
drug-to-lipid ratios of 0.002. Maximum PDT-induced leakage of
calcein from vesicles with a cell-like lipid composition coincubated
with ZnPC liposomes was observed at drug-to-lipid
ratios of 0.001.
Conclusion: Successful tumor growth was achieved for various
cell lines with different degrees of vascularization. Liposomes
developed for interstitial targeting were shown to fluoresce and
produce oxygen radicals, allowing the liposomes to be
concomitantly imaged and used for therapy. Further research will
focus on developing and characterizing liposomal formulations for
tumor cell and vascular targeting as well as on studying the PDT
efficacy of the formulations in vivo using the CAM models.