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盐酸特比萘芬纳米乳溶蚀性微针抑制β-1,3-葡聚糖酶的实验研究

Experimental research on fungal inhibition using dissolving microneedles of terbinafine hydrochloride nanoemulsion for beta-1,3-glucanase.

作者信息

Wang Huilin, Wang Yan, Liu Jianing, Qi Yonghua, Sun Weitong, Qiu Hongbin, Zhang Yu, Ping Yang

机构信息

College of Pharmacy, Jiamusi University Jiamusi 154007 Heilongjiang China

Heilongjiang University of Chinese Medicine Jiamusi College Jiamusi 154007 Heilongjiang China

出版信息

Nanoscale Adv. 2025 Jun 6. doi: 10.1039/d5na00163c.

Abstract

: Onychomycosis is characterized by high transmission and low recovery rates, leading to a lack of optimal treatments. This study used dissolving microneedles as drug carriers to design dual-loaded DMN patches with β-1,3-glucanase and terbinafine hydrochloride nanoemulsion. : Dissolving microneedles of terbinafine hydrochloride nanoemulsion for beta-1,3-glucanase (Gls-TBH-NE-DMN) were prepared using the centrifugal molding method. Parafilm®, weight method, mouse skin puncture experiments, and mouse skin tissue sections were used to evaluate the mechanical properties of Gls-TBH-NE-DMN. Gls-TBH-NE-DMN was tested for its anti- albicans susceptibility, ability to inhibit fungal cell wall synthesis, and fungal biofilm penetration and inhibition capabilities. The inhibitory effect of Gls-TBH-NE-DMN on fungi was studied using a rabbit nail infection model. : Gls-TBH-NE-DMN exhibited a penetration rate of 98% on skin simulants and a compressive bending resistance of 12.75%. It was nonirritating to the dorsal skin of mice, with no edema or erythema on the surface of the skin, suggesting a good safety profile. The accumulative release of Gls-TBH-NE-DMN at 72 h was 78.74% ± 0.64%, and that of terbinafine hydrochloride dissolving microneedles was 49.52% ± 0.80%. In the transdermal permeation experiment, the cumulative transdermal permeation of Gls-TBH-NE-DMN at 72 h was 73.21% ± 0.84% and that of terbinafine hydrochloride (TBH) was 20.57% ± 0.98%. inhibition of showed that the lowest inhibitory concentration in the Gls-TBH-NE-DMN group was 512 μg mL. Furthermore, experiments showed that Gls-TBH-NE-DMN could effectively inhibit fungal cell wall synthesis and disrupt the biofilm, inhibiting fungal growth. : Gls-TBH-NE-DMN prepared in this study provides new ideas for treating skin fungal diseases and for developing antimicrobial drug formulations.

摘要

甲癣的特点是传播率高而治愈率低,导致缺乏最佳治疗方法。本研究使用溶解微针作为药物载体,设计了负载β-1,3-葡聚糖酶和盐酸特比萘芬纳米乳剂的双负载溶解微针贴片。:采用离心成型法制备了用于β-1,3-葡聚糖酶的盐酸特比萘芬纳米乳剂溶解微针(Gls-TBH-NE-DMN)。使用Parafilm®、重量法、小鼠皮肤穿刺实验和小鼠皮肤组织切片来评估Gls-TBH-NE-DMN的机械性能。对Gls-TBH-NE-DMN进行了抗白色念珠菌敏感性、抑制真菌细胞壁合成的能力以及真菌生物膜穿透和抑制能力的测试。使用兔指甲感染模型研究了Gls-TBH-NE-DMN对真菌的抑制作用。:Gls-TBH-NE-DMN在皮肤模拟物上的渗透率为98%,抗压弯曲阻力为12.75%。它对小鼠背部皮肤无刺激性,皮肤表面无水肿或红斑,表明安全性良好。Gls-TBH-NE-DMN在72小时的累积释放率为78.74%±0.64%,盐酸特比萘芬溶解微针的累积释放率为49.52%±0.80%。在透皮渗透实验中,Gls-TBH-NE-DMN在72小时的累积透皮渗透率为73.21%±0.84%,盐酸特比萘芬(TBH)的累积透皮渗透率为20.57%±0.98%。抑制作用表明,Gls-TBH-NE-DMN组的最低抑菌浓度为512μg/mL。此外,实验表明Gls-TBH-NE-DMN可以有效抑制真菌细胞壁合成并破坏生物膜,抑制真菌生长。:本研究制备的Gls-TBH-NE-DMN为治疗皮肤真菌疾病和开发抗菌药物制剂提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ff/12282375/8736c83cdb4d/d5na00163c-f1.jpg

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