Thermosensitive nanocomposite gel loaded zinc phthalocyanine for photodynamic therapy

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ORIGINAL PAPER

Thermosensitive nanocomposite gel loaded zinc phthalocyanine for photodynamic therapy Min Yang 1 & Xiaoluan Lu 1 & Luyang Tang 1 & Yangyang Fu 1 & Peixin Yang 1 Received: 14 February 2020 / Accepted: 1 July 2020 # The Polymer Society, Taipei 2020

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. Keywords Thermosensitive hydrogel . Zn phthalocyanine . Mixed micelles . Rotation . Intermolecular collision . Photostability

Introduction Photodynamic therapy(PDT) is an alternative method based on the administration of a photosensitizer (PS) that sensitizes tumors to specific wavelength of light. It is harmless to use photosensitizer and light separately, but when combined, reactive singlet oxygen (1O2) are generated triggering (i) host immune response, (ii) localized ischaemia (iii) apoptosis and necrosis [1–3]. PDT is an approved minimally invasive therapeutic procedure for such as bladder, brain, breast, skin, and lung carcinomas [4, 5]. The advantages of using PDT include relatively low cost, low systemic toxicity, noninvasive resistance and fast healing with little

* Xiaoluan Lu [email protected] 1

School of Pharmacy, Guizhou University, Guiyang 550025, People’s Republic of China

or no scarring [1, 6]. However, Most PSs, such as phyrin, phthalocyanine and phenothiazine families, h