Transcutaneous application of ultrasound enhances the effects of finasteride in a murine model of androgenic alopecia

Abstract

Purpose: The purpose of this study was to evaluate if transcutaneous application of low-intensity ultrasound can locally enhance the effects of finasteride on hair growth in a murine model of androgenic alopecia (AA).Methods: AA mice (injected twice per week with testosterone enanthate, n=11), under daily oral administration of finasteride, received 1-MHz ultrasound for 1 hour at the unilateral thigh area five times per week for 5 weeks. Non-thermal and non-cavitational ultrasound was delivered in a pulsed manner (55-ms pulse duration with a repetition frequency of 4 Hz). Skin temperature was measured during sonication, and the measurements were validated with numerical simulations of sonication-induced tissue temperature changes. Hair growth was assessed both photographically and histologically.Results: We found more hair growth on the sonicated thigh area than on the unsonicated thigh, beginning from week 3 through the end of the experiment. Histological analyses showed that the number of hair follicles doubled in the skin sections that received sonication compared to the unsonicated zone, with thicker follicular diameter and skin. An over five-fold increase was also observed in the anagen/telogen ratio in the sonicated area, suggesting an enhanced anagen phase. Skin temperature was unaltered by the administered sonication.Conclusion: The findings of the present study suggest that pulsed application of ultrasound promotes hair growth, potentially by disrupting the binding of albumin to finasteride. This may suggest further applications to enhance the pharmacological effects of other relevant drugs exhibiting high plasma protein binding.

Network pharmacology analysis and experimental evaluations of YH complex on androgenetic alopecia by regulating the androgenic‐apoptotic axis

“…The percentage of hair follicles in anagen per telogen was markedly increased in YH complex‐treated mice. Regarding this, there are researches that topical application as well as oral administration of finasteride increased hair follicle anagen/telogen ratio (Kim et al., 2022). From those results, YH complex was found to have hair growing effects as similar as finasteride in AGA, although the components, doses, treatment period, and route are different.…”

Non-thermal Acoustic Enhancement of Chemotherapeutic Effects of Cisplatin on Xenografted Cervical Cancer in Mice

“…Considering a 50% duty cycle of sonication, the spatial-peak temporal-average intensity (I SPTA ) was 2.5 W/cm 2 . The use of a 50-ms pulse duration and a 10-Hz pulse repetition frequency was based on a non-thermal pulsing scheme that has been shown to unbind phenytoin from albumin at 250 kHz (12) and unbind lidocaine from α-1-acid glycoprotein at 500 kHz (13). Additional equilibrium dialysis cassettes were placed outside the sonication path (Figure 1E, 'FO') and in a region that was not exposed to sonication (Figure 1E, 'C' condition).…”

“…Application of non-ionizing, non-thermal mechanical force generated by pulsed low-intensity ultrasound pressure waves to the drug-plasma protein complex was found to temporarily disrupt PPB, consequently increasing the amount of unbound ('free') drug molecules available to the tissue without elevating the systemic concentration (12)(13)(14)(15). Investigations have revealed that acoustic pressure waves applied to a local region of tissue (of the order of 400 kPa) can impose a non-thermal radiation force greater than the binding force [Kim et al (13) for theoretical derivations for albumin and α-1-acid glycoprotein], leading to temporary unbinding of a drug from plasma proteins, which raises its 'effective' unbound concentration.…”