Sirirak Thanchanok, Subongkot Thirapit
Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand.
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand.
Pharmaceutics. 2025 Aug 5;17(8):1014. doi: 10.3390/pharmaceutics17081014.
: The present study aimed to synthesize folate-conjugated poloxamers and develop polymeric micelles for the dermal delivery of irinotecan and alpha-mangostin for the treatment of melanoma using poloxamer 188 and poloxamer 184, which have never been synthesized with folate before. : Poloxamer 188 and poloxamer 184 were synthesized with folate by esterification. The in vitro skin penetration enhancement of irinotecan- and alpha-mangostin-loaded folate-conjugated polymeric micelles was evaluated. The skin penetration pathway of folate-conjugated polymeric micelles was investigated by colocalization of multiple fluorescently labeled particles using confocal laser scanning microscopy (CLSM). : Folate-conjugated poloxamer 188 and poloxamer 184 were successfully synthesized. The prepared irinotecan- and alpha-mangostin-loaded folate-conjugated polymeric micelles from poloxamer 188 and poloxamer 184 had particle sizes of approximately 180 and 150 nm, respectively, indicating a positive charge with a narrow size distribution which could be easily taken up into cells. An in vitro skin penetration study revealed that folate-conjugated polymeric micelles from poloxamer 184 significantly enhanced the skin penetration of irinotecan and alpha-mangostin to a greater extent than the solution. CLSM visualization revealed that folate-conjugated polymeric micelles penetrated through the skin by the transfollicular pathway as the major penetration pathway, whereas penetration by the intercluster pathway, transcellular pathway and intercellular pathway constituted a minor pathway. : Folate-conjugated poloxamer 184 polymeric micelles are promising candidates for the dermal delivery of anticancer drugs by the transfollicular pathway as the major skin penetration pathway.
本研究旨在合成叶酸共轭泊洛沙姆，并开发用于伊立替康和α-山竹素经皮递送以治疗黑色素瘤的聚合物胶束，使用的是泊洛沙姆188和泊洛沙姆184，此前从未将它们与叶酸进行合成。通过酯化反应将叶酸与泊洛沙姆188和泊洛沙姆184进行合成。评估了负载伊立替康和α-山竹素的叶酸共轭聚合物胶束的体外皮肤渗透增强作用。使用共聚焦激光扫描显微镜（CLSM）通过多种荧光标记颗粒的共定位研究了叶酸共轭聚合物胶束的皮肤渗透途径。成功合成了叶酸共轭泊洛沙姆188和泊洛沙姆184。由泊洛沙姆188和泊洛沙姆184制备的负载伊立替康和α-山竹素的叶酸共轭聚合物胶束的粒径分别约为180和150nm，表明带正电荷且粒径分布窄，能够容易地被细胞摄取。体外皮肤渗透研究表明，泊洛沙姆184的叶酸共轭聚合物胶束比溶液更显著地增强了伊立替康和α-山竹素的皮肤渗透。CLSM可视化显示，叶酸共轭聚合物胶束通过经毛囊途径作为主要渗透途径穿透皮肤，而通过簇间途径、跨细胞途径和细胞间途径的渗透构成次要途径。叶酸共轭泊洛沙姆184聚合物胶束有望作为主要皮肤渗透途径经毛囊途径用于抗癌药物的经皮递送。
