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In Vivo Assessment of Thermosensitive Liposomes for the Treatment of Port Wine Stains by Antifibrinolytic Site-Specific Pharmaco-Laser Therapy
- Source :
- Pharmaceutics, 12(6):591. Multidisciplinary Digital Publishing Institute (MDPI), Pharmaceutics, 12(6):591, 1-27. MDPI Multidisciplinary Digital Publishing Institute, Pharmaceutics, Pharmaceutics, 12(6). American Chemical Society, Volume 12, Issue 6, Pharmaceutics, Vol 12, Iss 591, p 591 (2020)
- Publication Year :
- 2020
-
Abstract
- Antifibrinolytic site-specific pharmaco-laser therapy (SSPLT) is an experimental treatment modality for refractory port wine stains (PWS). Conceptually, antifibrinolytic drugs encapsulated in thermosensitive liposomes are delivered to thrombi that form in semi-photocoagulated PWS blood vessels after conventional laser treatment. Local release of antifibrinolytics is induced by mild hyperthermia, resulting in hyperthrombosis and complete occlusion of the target blood vessel (clinical endpoint). In this study, 20 thermosensitive liposomal formulations containing tranexamic acid (TA) were assayed for physicochemical properties, TA:lipid ratio, encapsulation efficiency, and endovesicular TA concentration. Two candidate formulations (DPPC:DSPE-PEG, DPPC:MPPC:DSPE-PEG) were selected based on optimal properties and analyzed for heat-induced TA release at body temperature (T), phase transition temperature (Tm), and at T &gt<br />Tm. The effect of plasma on liposomal stability at 37 &deg<br />C was determined, and the association of liposomes with platelets was examined by flow cytometry. The accumulation of PEGylated phosphocholine liposomes in laser-induced thrombi was investigated in a hamster dorsal skinfold model and intravital fluorescence microscopy. Both formulations did not release TA at 37 &deg<br />C. Near-complete TA release was achieved at Tm within 2.0&ndash<br />2.5 min of heating, which was accelerated at T &gt<br />Tm. Plasma exerted a stabilizing effect on both formulations. Liposomes showed mild association with platelets. Despite positive in vitro results, fluorescently labeled liposomes did not sufficiently accumulate in laser-induced thrombi in hamsters to warrant their use in antifibrinolytic SSPLT, which can be solved by coupling thrombus-targeting ligands to the liposomes.
- Subjects :
- Tranexamic acid
PULSED DYE-LASER
circulation time
lcsh:RS1-441
Pharmaceutical Science
02 engineering and technology
fluorescent thrombus staining
release
targeted drug delivery
chemistry.chemical_compound
PHOTODYNAMIC THERAPY
0302 clinical medicine
Platelet
VITRO
DRUG-DELIVERY
vascular malformations
intravital fluorescence microscopy
Phosphocholine
lipid monolayers
Liposome
Targeted drug delivery
Chemistry
SELECTIVE PHOTOTHERMOLYSIS
021001 nanoscience & nanotechnology
hyperthermia
Fluorescent thrombus staining
030220 oncology & carcinogenesis
Drug delivery
Intravital fluorescence microscopy
0210 nano-technology
medicine.drug
Hyperthermia
Endovascular laser-tissue interactions
Antifibrinolytic
medicine.drug_class
Vascular malformations
Article
tranexamic acid
lcsh:Pharmacy and materia medica
03 medical and health sciences
In vivo
endovascular laser-tissue interactions
medicine
thrombosis
pegylated lecithin liposomes
Chromatography
Thrombosis
medicine.disease
Subjects
Details
- Language :
- English
- ISSN :
- 19994923 and 15438384
- Database :
- OpenAIRE
- Journal :
- Pharmaceutics, 12(6):591. Multidisciplinary Digital Publishing Institute (MDPI), Pharmaceutics, 12(6):591, 1-27. MDPI Multidisciplinary Digital Publishing Institute, Pharmaceutics, Pharmaceutics, 12(6). American Chemical Society, Volume 12, Issue 6, Pharmaceutics, Vol 12, Iss 591, p 591 (2020)
- Accession number :
- edsair.doi.dedup.....f0ae7c675cacc9d016dbb86e96269422