Thermosensitive nanocomposite gel loaded zinc phthalocyanine for photodynamic therapy

Abstract

The purpose of this work was first to propose a thermosensitive hydrogel incorporating Zn phthalocyanine loaded mixed micelles for drug delivery. The mixed micelles was prepared easily by dialysis method and the thermosensitive hydrogel was prepared by “cold method” using Pluronic F127 as hydrogel matrix. The properties of sol and gel transition caused by F127 temperature response enables the drug loaded micellar hydrogel(DLM-Gel) to gel in situ gelification upon injection providing long-term retention within the tumor. Sodium deoxycholate (SDC) and D-alpha tocopheryl polyethylene glycol succinate (TPGS) were utilized as micelles materials. Micelles resulted in a mean particle size around 106 nm, spherical morphology and loading efficiency up to 92%. The DLM-Gel displayed a three-dimensional network structure, which helps to stabilize ZnPc molecules because it can reduce the rotation and intermolecular collision of the ZnPc molecules, leading to the enhancement of fluorescence intensity and 1O2 generation. The production of 1O2 from DLM-Gel was more efficient than micelles under the same laser irradiation condition. The DLM-Gel was more photostable than free ZnPc and micelles in the timescale typically used in photodynamic therapy(PDT), only a small photobleaching event(16.91%) was observed after 20 min of light irradiation. Rheology studies demonstrated that DLM-Gel has the potential to be injected at room temperature and to adapt to the deformation of surrounding tissues during human motion. The in vitro drug release studies of DLM-Gel demonstrated slower drug release than mixed micelles. Phototoxicity experiments in A549 cells showed that DLM-Gel had significante toxicity.Therefore the injective micellar hydrogels is a potential drug delivery system for PDT.