Faculty of Pharmacy, Kindai University, Osaka 577-8502, Japan.
Research & Development Laboratories Self-Medication, Taisho Pharmaceutical Co., Ltd., Saitama 331-9530, Japan.
Int J Nanomedicine. 2019 Oct 1;14:7921-7931. doi: 10.2147/IJN.S225496. eCollection 2019.
We designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice.
N-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively.
The ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90-300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD.
We designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).
我们设计了基于米诺地尔(MXD)纳米颗粒(N-MXD)的配方,并研究了 N-MXD 是否可以增加药物向毛囊的输送。此外,我们还研究了 N-MXD 对 C57BL/6 小鼠毛发生长的影响。
制备 1%的 N-MXD:甲基纤维素、对羟基烷酸酯、甘露醇和 MXD 分散在纯化水中,在冷藏条件下(5500rpm,30s×15 次,间歇研磨)用氧化锆珠研磨。使用 C57BL/6 小鼠评估毛发生长效果。通过实时 PCR 和 ELISA 方法分别测定血管内皮生长因子(VEGF)和胰岛素样生长因子-1(IGF-1)的 mRNA 和蛋白表达水平。
N-MXD 中固体-MXD 的比例约为 60%,而 MXD 纳米颗粒(90-300nm)呈长形。对于纳米药物的设计,可用性很重要。因此,我们测量了 N-MXD 处理后的稳定性和毒性。在 2 周内未检测到 MXD 纳米颗粒的聚集,并且在重复应用 N-MXD 后皮肤无红肿或 MXD 粉末残留。接下来,我们通过 N-MXD 处理评估毛发生长效果。N-MXD 皮肤组织中的 MXD 含量低于市售 MXD 制剂(CA-MXD)。相反,N-MXD 毛囊中的 MXD 含量高于 CA-MXD,N-MXD 的药物疗效也高于 CA-MXD。此外,IGF-1 和 VEGF 的 mRNA 和蛋白水平通过 N-MXD 和 CA-MXD 的重复应用得到增强,并且 N-MXD 增强的 IGF-1 和 VEGF 水平明显高于 CA-MXD。
我们设计了一种基于 MXD 纳米颗粒的新型纳米药物,并表明 N-MXD 可以通过毛囊将 MXD 输送到毛囊中,并且对毛发生长的治疗效率高于 CA-MXD(溶液型)。