Abstract
Poly-γ-glutamic acid (γ-PGA)-based nanoparticles draw remarkable attention as drug delivery agents due to their controlled release characteristics, low toxicity, and biocompatibility. 4HGF is an herbal mixture of Phellinus linteus grown on germinated brown rice, Cordyceps militaris grown on germinated soybeans, Polygonum multiflorum, Ficus carica, and Cocos nucifera oil. Here, we encapsulated 4HGF within PGA-based hydrogel nanoparticles, prepared by simple ionic gelation with chitosan, to facilitate its penetration into hair follicles (HFs). In this study, we report the hair promoting activity of 4HGF encapsulated with PGA nanoparticles (PGA-4HGF) and their mechanism, compared to 4HGF alone. The average size of spherical nanoparticles was ~400 nm in diameter. Continuous release of PGA-4HGF was observed in a simulated physiological condition. As expected, PGA-4HGF treatment increased hair length, induced earlier anagen initiation, and elongated the duration of the anagen phase in C57BL/6N mice, compared with free 4HGF treatment. PGA-4HGF significantly increased dermal papilla cell proliferation and induced cell cycle progression. PGA-4HGF also significantly increased the total amount of β-catenin protein expression, a stimulator of the anagen phase, through induction of cyclinD1 and CDK4 protein levels, compared to free 4HGF treatment. Our findings underscore the potential of PGA nanocapsules to efficiently deliver 4HGF into HFs, hence promoting hair-growth. Therefore, PGA-4HGF nanoparticles may be promising therapeutic agents for hair growth disorders.
Highlights
Alopecia, known as hair loss, is a condition caused by various factors such as hormone imbalance, stress, malnutrition, and chemotherapy [1,2,3]
We explored a mixture of herbal extracts (4HGF) including Phellinus linteus grown on germinated brown rice, Cordyceps militaris grown on germinated soybeans, Polygonum multiflorum, Ficus carica, and Cocos nucifera oil
P. linteus grown on germinated brown rice [11], C. militaris grown on germinated soybeans [12,13], and F. carica [14] possess anti-inflammatory properties relevant to promoting hair growth
Summary
Known as hair loss, is a condition caused by various factors such as hormone imbalance, stress, malnutrition, and chemotherapy [1,2,3]. To determine the hair-growth promoting effect of PGA-4HGF in telogenic C57BL/6N mice, PGA-4HGF was topically applied on the shaved dorsal skin (Figure 3A). By day 12, black areas were more prominent in the PGA-4HGF treated dorsal skins, compared with those in the non-treated control or PGA-control groups (Figure 3B). By day 12, the regrown hair lengths of the PGA-4HGF treated group were 1.2-fold longer, compared with that of 4HGF group (Figure 4C). Our results indicate that PGA-4HGF induced hair-growth compared with the non-treated control and PGA-control groups and 4HGF groups. DC0y.c7l4in±D0.102a,nrdesCpeDctKiv4eplyr)ogtreoinupex(Fpirgeusrseio6nB)l.evels were increased in the PGA-4HGF-treated group (1.36 ± 0.08 and 1.38 ± 0.07, respectively), compared with the 4HGF (0.73 ± 0.03 and 0.74 ± 0.02, respectively) group (Figure 6B) TThhee pisrooetleeicntriscpots detectepdoifnrto(mpI)2sDepgaeralstioanndwaans adloynzeedfrobmy pthHe 4PDtoQ8.uTehste(mveorlesciounlar7.w0,eiBgihotR(Mad.w) st)osftewpaarraeti.oTnhweaissodeolneectric point (fprIo)mse5p0a–r7a0tkioDna.w(Cas) TdhoenseeflreoctmedpsHpo4tstwo e8r.eTahnealmyzoeldecuuslianrgwpeepigtihdte(mMa.swstf)insgeepraprraintitoinngw(PaMs dF)o.ne from 50–70 kDa. (C) The selected spots were analyzed using peptide mass fingerprinting (PMF)
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