Croconium Dye Thermosensitive Liposomes for Light Activated Drug Release

Abstract

This study investigates a novel light-activated drug delivery system designed to produce on-demand drug release. The light-activated system was developed by incorporating a photostable photothermal agent, croconium dye, into liposomes to enable thermally triggered drug release. The drug release from the liposomes was determined at three powers of 210, 295, and 380 mW under 0-, 1-, and 2-minute light irradiation. A continuous wave 808 nm laser was used as the light source. Dexamethasone sodium phosphate (DSP) released from the liposomes was tunable depending on the power and irradiation time with a range of 1 -19 g released depending on irradiation power and time. For local temperature measurement during the photothermal activation, polymerized 10, 12 - Pentacosadiynoic acid (PCDA) was incorporated in the lipid bilayer. Under heating polymerized PCDA undergoes a transition into a red phase from a blue phase. Utilizing the spectrum changes under known temperatures a regression model was developed to calculate the local temperature of the liposomes under irradiation. The ability of the liposomes to release DSP under irradiation in the presence of a phantom tissue was tested under different attenuation coefficients to match various common biological tissues. The liposomes were still able to release DSP in the presence of tissue phantoms for a certain thickness of the tissue. Finally, the cytotoxicity of the liposomes with the croconium dye for chemical and thermal toxicity was determined. The liposomes displayed good biocompatibility with Human Microvascular Endothelial Cell line-1 (HMEC-1). The results support the use of croconium dye as a potential alternative to commonly photothermal agents used in drug delivery such as metal nanoparticles. Future work will focus on optimization of absorbance spectrum for drug release, and in vivo studies for efficacy and safety.