@article{8e6e5471a0dd415fb5928b55b494116a,
title = "In Vivo Assessment of Thermosensitive Liposomes for the Treatment of Port Wine Stains by Antifibrinolytic Site-Specific Pharmaco-Laser Therapy",
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 (T-m), and at T > T-m. The effect of plasma on liposomal stability at 37 degrees 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 degrees C. Near-complete TA release was achieved at T(m)within 2.0-2.5 min of heating, which was accelerated at T > T-m. 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.",
keywords = "circulation time, drug-delivery, endovascular laser-tissue interactions, fluorescent thrombus staining, hyperthermia, intravital fluorescence microscopy, lipid monolayers, pegylated lecithin liposomes, photodynamic therapy, pulsed dye-laser, release, selective photothermolysis, targeted drug delivery, thrombosis, tranexamic acid, vascular malformations, vitro, DRUG-DELIVERY, PEGYLATED LECITHIN LIPOSOMES, PULSED DYE-LASER, SELECTIVE PHOTOTHERMOLYSIS, VITRO, PHOTODYNAMIC THERAPY, LIPID MONOLAYERS, RELEASE, TRANEXAMIC ACID, CIRCULATION TIME",
author = "M.J. Li and {van Raath}, M.I. and S. Khakpour and A. Secilir and B.C. Sliggers and X. Huang and B.Y. Ding and G. Storm and {van der Hulst}, R.R. and {de Kroon}, A.I.P.M. and M. Heger",
note = "Funding Information: This project was supported by a Stichting Technologische Wetenschap (STW) valorisation grant (# 12064) and a preseed grant from the Academic Medical Center SKE Fund (Technostarter #20090812) to MH as well as a Basic Public Welfare Research Project of Zhejiang Province (No. LGF18H160034, No. LGD20H300001) to BD. MH is currently supported by grants from the Dutch Cancer Foundation (KWF project #10666), National Natural Science Foundation of China (#81872220), a Zhejiang Provincial Foreign Expert Program Grant, Zhejiang Provincial Key Natural Science Foundation of China (#Z20H160031), and a grant for the establishment of the Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics. Site-specific pharmaco-laser therapy was patented (M. Heger. Drug delivery system for use in the treatment of vascular and vessel-related pathologies; EP09151332.5, PCT/EP2010/050833). MH is co-founder of Nurish.Me and has equity in that company (whose business activities are unrelated to the present work). Funding Information: Funding: This project was supported by a Stichting Technologische Wetenschap (STW) valorisation grant (# 12064) and a preseed grant from the Academic Medical Center SKE Fund (Technostarter #20090812) to MH as well as a Basic Public Welfare Research Project of Zhejiang Province (No. LGF18H160034, No. LGD20H300001) to BD. MH is currently supported by grants from the Dutch Cancer Foundation (KWF project #10666), National Natural Science Foundation of China (#81872220), a Zhejiang Provincial Foreign Expert Program Grant, Zhejiang Provincial Key Natural Science Foundation of China (#Z20H160031), and a grant for the establishment of the Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics. Site-specific pharmaco-laser therapy was patented (M. Heger. Drug delivery system for use in the treatment of vascular and vessel-related pathologies; EP09151332.5, PCT/EP2010/050833). MH is co-founder of Nurish.Me and has equity in that company (whose business activities are unrelated to the present work). Publisher Copyright: {\textcopyright} 2020 by the authors.",
year = "2020",
month = jun,
day = "1",
doi = "10.3390/pharmaceutics12060591",
language = "English",
volume = "12",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",
}