Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia 30341, USA.
Pharm Res. 2012 Aug;29(8):2092-103. doi: 10.1007/s11095-012-0738-0. Epub 2012 Mar 27.
To engineer optimized near-infrared (NIR) active thermosensitive liposomes to potentially achieve image-guided delivery of chemotherapeutic agents.
Thermosensitive liposomes were surface-coated with either polyethylene glycol or dextran. Differential scanning calorimetry and calcein release studies were conducted to optimize liposomal release, and flow cytometry was employed to determine the in vitro macrophage uptake of liposomes. Indocyanine green (ICG) was encapsulated as the NIR dye to evaluate the in vivo biodistribution in tumor-bearing mice.
The optimized thermosensitive liposome formulation consists of DPPC, SoyPC, and cholesterol in the 100:50:30 molar ratio. Liposomes with dextran and polyethylene glycol demonstrated similar thermal release properties; however in vitro macrophage uptake was greater with dextran. Non-invasive in vivo NIR imaging showed tumor accumulation of liposomes with both coatings, and ex vivo NIR imaging correlated well with actual ICG concentrations in various organs of healthy mice.
The optimized thermosensitive liposome formulation demonstrated stability at 37 °C and efficient burst release at 40 and 42 °C. Dextran exhibited potential for application as a surface coating in thermosensitive liposome formulations. In vivo studies suggest that liposomal encapsulation of ICG permits reliable, real-time monitoring of liposome biodistribution through non-invasive NIR imaging.
设计优化的近红外（NIR）活性热敏脂质体，以潜在实现化疗药物的图像引导递药。
热敏脂质体表面涂覆聚乙二醇或葡聚糖。通过差示扫描量热法和钙黄绿素释放研究优化脂质体释放，采用流式细胞术测定脂质体在体外巨噬细胞中的摄取。吲哚菁绿（ICG）被包裹作为 NIR 染料，以评估荷瘤小鼠体内的生物分布。
优化的热敏脂质体配方由 DPPC、大豆卵磷脂和胆固醇以 100:50:30 的摩尔比组成。具有葡聚糖和聚乙二醇的脂质体具有相似的热释放特性；然而，葡聚糖的体外巨噬细胞摄取更高。非侵入性体内近红外成像显示两种涂层的脂质体在肿瘤中的积累，并且离体近红外成像与健康小鼠各器官中实际 ICG 浓度的相关性良好。
优化的热敏脂质体配方在 37°C 时表现出稳定性，在 40°C 和 42°C 时表现出高效的爆发释放。葡聚糖显示出作为热敏脂质体配方表面涂层的应用潜力。体内研究表明，ICG 的脂质体包封允许通过非侵入性近红外成像可靠、实时监测脂质体的生物分布。
