研究 N-甲基葡糖胺锑（Sb）联合脂质体氯铝酞菁光动力疗法治疗 C57BL6 小鼠感染利什曼原虫（L.）引起的皮肤利什曼病的疗效。
Study of the efficacy of N-methyl glucamine antimoniate (Sb) associated with photodynamic therapy using liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL6 mice.
机构信息
Faculty of Medicine, Dermatomycology Laboratory, University of Brasília, Campus Darcy Ribeiro, 70910-900 Brasília/DF, Brazil.
Institute of Biological Sciences, Department of Genetics and Morphology, University of Brasília, Campus Darcy Ribeiro, 70910-900, Brasília/DF, Brazil.
出版信息
Photodiagnosis Photodyn Ther. 2019 Jun;26:261-269. doi: 10.1016/j.pdpdt.2019.04.004. Epub 2019 Apr 2.
BACKGROUND
Pentavalent antimonials remain first-line drugs in the treatment of cutaneous leishmaniasis (CL); however, adverse effects and drug resistance have led to the search for less toxic and more effective treatments. As an alternative, topical phthalocyanine has been studied and its efficacy and low toxicity demonstrated. We aimed to study the in vivo efficacy of N-methyl glucamine antimoniate (NMG) associated with photodynamic therapy (PDT) with topical liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of experimental CL by L. amazonensis.
METHODS
Experimental study with 54 C57BL6 isogenic mice divided into 9 groups including uninfected control, untreated control, PDT with AlClPC + NMG at doses of 10 and 20 mgSb/Kg/day. The criteria to evaluate the treatment efficacy were: paw diameter, amastigote count, culture, viability test and parasite counts using MTT (3-bromo-4,5-dimethylthiazol-2,5-diphenyl-tetrazolium bromide).
RESULTS
Treatment of CL with the association of NMG20 + PDT with AlClPC showed significant reduction of paw diameter, amastigote count, cultures, viability test and parasite counts. Parasite reduction occurred at the 10th and 20th days of treatment and 60 days after treatment ended, indicating that parasites did not multiply again. The NMG10 + PDT group with AlClPC presented results equivalent to gold-standard treatment (20 mgSb/kg/day). Biochemical and histopathological evaluation showed minor changes.
CONCLUSION
Treatment of CL caused by L. amazonensis with NMG20 mgSb/kg/day + PDT with AlClPC was more effective than the traditional NMG20 mgSb/kg/day.
背景
五价锑剂仍然是治疗皮肤利什曼病（CL）的一线药物；然而，不良反应和耐药性导致人们寻求毒性更小、更有效的治疗方法。作为替代方法，局部酞菁已被研究，其疗效和低毒性已得到证实。我们旨在研究 N-甲基葡糖胺锑（NMG）与局部脂质体氯铝酞菁（AlClPC）光动力疗法（PDT）联合治疗 L. amazonensis 引起的实验性 CL 的体内疗效。
方法
对 54 只 C57BL6 同基因小鼠进行实验研究，分为 9 组，包括未感染对照组、未治疗对照组、用 10 和 20mgSb/Kg/天剂量的 NMG+PDT 治疗的 AlClPC 组。评估治疗效果的标准是：爪直径、前鞭毛体计数、培养、 viability 试验和使用 MTT（3-溴-4,5-二甲基噻唑-2,5-二苯基四氮唑溴化物）的寄生虫计数。
结果
用 NMG20+PDT 联合 AlClPC 治疗 CL，爪直径、前鞭毛体计数、培养物、 viability 试验和寄生虫计数明显减少。在治疗的第 10 天和第 20 天以及治疗结束后 60 天，寄生虫数量减少，表明寄生虫不再繁殖。NMG10+PDT 联合 AlClPC 组的治疗效果与金标准治疗（20mgSb/kg/天）相当。生化和组织病理学评估显示出较小的变化。
结论
用 NMG20mgSb/kg/天+PDT 联合 AlClPC 治疗 L. amazonensis 引起的 CL 比传统的 NMG20mgSb/kg/天更有效。
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