Effects of nanoparticles of hydroxy-aluminum phthalocyanine on markers of liver injury and glucose metabolism in diabetic mice

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.

光动力疗法（Photodynamic Therapy）通过减轻疼痛与炎症、促进健康细胞增殖，可用于治疗复发性病灶，例如糖尿病足溃疡（Diabetic Foot Ulcers）。采用光敏剂（photosensitizer）酞菁（phthalocyanine），联合Pluronic®与Carbopol®构建的纳米结构共聚基质，用于治疗糖尿病足溃疡与利什曼病（leishmaniosis）病灶的相关研究，已展现出积极的应用前景。尽管这类制剂采用外用或皮下给药方式，但其中的活性分子仍可被机体吸收，其全身效应尚未明确。因此本研究以1型糖尿病瑞士品系小鼠为模型，探究了无需光照的羟基铝酞菁水凝胶皮下给药对全身参数、肝损伤标志物及肝脏能量代谢的影响。无论是该水凝胶还是不同剂量的酞菁，均会改变肝损伤标志物水平与肝脏葡萄糖释放量，有时甚至会加重糖尿病本身引发的代谢紊乱。但2.23 μg/mL剂量组仅引发程度较轻的血浆与代谢改变，且未改变糖尿病小鼠的葡萄糖耐量（glucose tolerance）与胰岛素敏感性（insulin sensitivity）。上述结果表明，羟基铝酞菁水凝胶用于治疗糖尿病患者皮肤溃疡的全身安全性良好。