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 > Tm. The effect of plasma on liposomal stability at 37 °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 °C. Near-complete TA release was achieved at Tm within 2.0–2.5 min of heating, which was accelerated at T > 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.
Highlights
Port wine stains (PWS) are congenital lesions in the skin that are comprised of ectatic venule-like vasculature [1,2]
The goal is to formulate thermosensitive liposomes with maximum tranexamic acid (TA) encapsulation so that a heat-induced antifibrinolytic environment can be realized in PWS blood vessels with a minimum number of locally accumulated liposomes
In our preceding study [16], two of six liposomal formulations were deemed candidates for antifibrinolytic site-specific pharmaco-laser therapy (SSPLT) based on their physicochemical properties and release kinetics in buffered solution
Summary
Port wine stains (PWS) are congenital lesions in the skin that are comprised of ectatic venule-like vasculature [1,2]. Due to extensive density and abnormally large blood volume, the hyperdilated blood vessels cause the skin to appear red-to-purple [3]. Photocoagulated blood vessels are subsequently removed by wound healing mechanisms and replaced by normal-sized capillaries, which coincides with a reduction in vascular density, blood volume, and lesional redness [7]. These processes are only effective in completely photocoagulated blood vessels [8], achieved in approximately half of the laser-treated patients [9,10]. The numerous innovations and ancillary interventions in laser treatment of PWS have not translated to improved clinical outcomes during the last three decades [9,10], altogether creating a strong medical need for novel, more effective treatment modalities [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
