International Journal of Nanomedicine (2019-10-01)

Drug Delivery System Based On Minoxidil Nanoparticles Promotes Hair Growth In C57BL/6 Mice

  • Nagai N,
  • Iwai Y,
  • Sakamoto A,
  • Otake H,
  • Oaku Y,
  • Abe A,
  • Nagahama T

Journal volume & issue
Vol. Volume 14
pp. 7921 – 7931

Abstract

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Noriaki Nagai,1 Yoshie Iwai,1 Akane Sakamoto,1 Hiroko Otake,1 Yoshihiro Oaku,2 Akinari Abe,2 Tohru Nagahama2 1Faculty of Pharmacy, Kindai University, Osaka 577-8502, Japan; 2Research & Development Laboratories Self-Medication, Taisho Pharmaceutical Co., Ltd., Saitama 331-9530, JapanCorrespondence: Noriaki NagaiFaculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, JapanTel +81 6 4307 3640Fax +81 6 6730 1394Email [email protected]: 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.Methods: 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.Results: 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.Conclusion: 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).Keywords: minoxidil, nanoparticle, androgenetic alopecia, hair follicle delivery, hair growth

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