Epidemiology shows that alopecia afflicts about half of the adult population worldwide and has become an important health problem affecting the daily lives of the general public. Due to the complexity of the etiology alopecia and the limited number of available treatments, it is important to develop efficient and safe treatment options. In this study, dutasteride (DUT) nanovesicles (NV@DUT) with egg yolk lecithin, oleic acid and vitamin E polyethylene glycol succinate were constructed, aiming to enhance the skin penetration and retention of DUT while having multiple coordinated effects of antioxidation and anti-inflammation, thereby improving the therapeutic effect. NV@DUT has a slightly milky luster, with a particle size of about 141.3 ± 0.45 nm, uniformly dispersed, its polydispersity index (PDI) is 0.17 ± 0.003. After 60 days of placement at room temperature with small changes in particle size and PDI. Compared with free DUT, the transdermal penetration and skin retention of the drug in NV@DUT increased by approximately 1.7 times. In vitro results showed that NV@DUT has antioxidant and anti-inflammatory activity. At 500 μg·mL-1 NV@DUT, the scavenging rate of radicals was about 50%, and the inhibition rate of nitric oxide production was about 50%, it improves the homeostasis of the hair follicle microenvironment. In addition, at 20 μg·mL-1 NV@DUT can promote the proliferation and migration of dermal papilla cells (HDPCs) and human umbilical vein endothelial cells (HUVECs), the cell viability were (132.67 ± 4.14)% and (116.64 ± 5.14)%; the migration rates were (84.68 ± 3.31)% and (61.87 ± 4.23)%. A preliminary investigation of its mechanism revealed that NV@DUT up-regulate the mRNA expression of β-catenin, vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and down-regulation the mRNA expression of type II 5 alpha-reductase (SRD5A2). NV@DUT can also promote hair regrowth in mice with androgenetic alopecia (AGA), and the weight of the new hair and the thickness of the skin in the mice were higher than those in the model group and the DUT group. The animal experiments were approved by the Laboratory Animal Ethics Committee of Sun Yat-Sen University, and all experiments were conducted in accordance with relevant guidelines and regulations. Approval number: 2022000828. The experimental results show that NV@DUT can treat AGA through multiple mechanisms and pathways, providing a new therapeutic strategy for alopecia.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |