de Lima Sarah Kymberly Santos, Cavallone Ítalo Novaes, Serrano Dolores Remedios, Anaya Brayan J, Lalatsa Aikaterini, Laurenti Márcia Dalastra, Lago João Henrique Ghilardi, da Silva Souza Dalete Christine, Marinsek Gabriela Pustiglione, Lopes Beatriz Soares, de Britto Mari Renata, Passero Luiz Felipe Domingues
Institute of Biosciences, São Paulo State University (UNESP), Praça Infante Dom Henrique, s/n, São Vicente 11330-900, SP, Brazil.
Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, São Paulo University, São Paulo 01246-903, SP, Brazil.
Pharmaceutics. 2023 Nov 8;15(11):2602. doi: 10.3390/pharmaceutics15112602.
Cutaneous leishmaniasis exhibits a wide spectrum of clinical manifestations; however, only a limited number of drugs are available and include Glucantime and amphotericin B, which induce unacceptable side effects in patients, limiting their use. Thus, there is an urgent demand to develop a treatment for leishmaniasis. Recently, it was demonstrated that 8-hydroxyquinoline (8-HQ) showed significant leishmanicidal effects in vitro and in vivo. Based on that, this work aimed to develop a topical formulation containing 8-HQ and assess its activity in experimental cutaneous leishmaniasis. 8-HQ was formulated using a Beeler base at 1 and 2% and showed an emulsion size with a D of 25 and 51.3 µm, respectively, with a shear-thinning rheological behaviour. The creams were able to permeate artificial Strat-M membranes and excised porcine skin without causing any morphological changes in the porcine skin or murine skin tested. In BALB/c mice infected with , topical treatment with creams containing 1 or 2% of 8-HQ was found to reduce the parasite burden and lesion size compared to infected controls with comparable efficacy to Glucantime (50 mg/kg) administered at the site of the cutaneous lesion. In the histological section of the skin from infected controls, a diffuse inflammatory infiltrate with many heavily infected macrophages that were associated with areas of necrosis was observed. On the other hand, animals treated with both creams showed only moderate inflammatory infiltrate, characterised by few infected macrophages, while tissue necrosis was not observed. These histological characteristics in topically treated animals were associated with an increase in the amount of IFN-γ and a reduction in IL-4 levels. The topical use of 8-HQ was active in decreasing tissue parasitism and should therefore be considered an interesting alternative directed to the treatment of leishmaniasis, considering that this type of treatment is non-invasive, painless, and, importantly, does not require hospitalisation, improving patient compliance by allowing the treatment to be conducted.
皮肤利什曼病表现出广泛的临床表现；然而，可用的药物数量有限，包括葡糖胺锑钠和两性霉素B，这些药物会在患者身上引起难以接受的副作用，限制了它们的使用。因此，迫切需要开发一种治疗利什曼病的方法。最近，有研究表明8-羟基喹啉（8-HQ）在体外和体内均显示出显著的杀利什曼原虫作用。基于此，本研究旨在开发一种含8-HQ的外用制剂，并评估其在实验性皮肤利什曼病中的活性。8-HQ采用Beeler基质分别配制成1%和2%的制剂，乳液粒径的D值分别为25和51.3 µm，具有剪切变稀的流变学行为。这些乳膏能够渗透人工Strat-M膜和切除的猪皮肤，且不会对所测试的猪皮肤或鼠皮肤造成任何形态学变化。在感染了[具体病原体未给出]的BALB/c小鼠中，发现用含1%或2% 8-HQ的乳膏进行局部治疗可减轻寄生虫负荷和病变大小，与在皮肤病变部位给予葡糖胺锑钠（50 mg/kg）的感染对照组相比，疗效相当。在感染对照组的皮肤组织切片中，观察到弥漫性炎性浸润，有许多严重感染的巨噬细胞，且与坏死区域相关。另一方面，用两种乳膏治疗的动物仅表现出中度炎性浸润，其特征为少量感染的巨噬细胞，未观察到组织坏死。局部治疗动物的这些组织学特征与IFN-γ量的增加和IL-4水平的降低有关。8-HQ的局部应用在减少组织寄生虫感染方面具有活性，因此应被视为治疗利什曼病的一种有吸引力的替代方法。考虑到这种治疗方式是非侵入性的、无痛的，而且重要的是不需要住院，通过允许进行治疗提高了患者的依从性。
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