Abstract
Ultrasound (US) has been found to rejuvenate and invigorate the hair follicles, increase the size of hair shafts, and promote new hair growth. Our present study found that dual-frequency US-mediated microbubble (MB) cavitation significantly enhanced minoxidil (Mx) delivery in both in vitro and in vivo models, while increasing the hair growth efficacy compared to single-frequency US sonication. The in vitro experiments showed that cavitation activity was enhanced more significantly during dual-frequency sonication than single-frequency sonication in higher concentration of MBs. The pigskin penetration depth in the group in which dual-frequency US was combined with MBs was 1.54 and 2.86 times greater than for single-frequency US combined with MBs and in the control group, respectively; the corresponding increases in the release rate of Mx at 18 hours in in vitro Franz-diffusion-cell experiments were 24.9% and 43.7%. During 21 days of treatment in C57BL/6J mice experiments, the growth rate at day 11 in the group in which dual-frequency US was combined with MBs increased by 2.07 times compared to single-frequency US combined with MBs. These results indicate that dual-frequency US-mediated MB cavitation can significantly increase both skin permeability and transdermal drug delivery. At the same US power density, hair growth was greater in the group with dual-frequency US plus MBs than in the group with single-frequency US plus MBs, without damaging the skin in mice.
Highlights
Ultrasound (US) has been found to rejuvenate and invigorate the hair follicles, increase the size of hair shafts, and promote new hair growth
Our previous study demonstrated that dual- or multiple-frequency US wave irradiations are possible to be generated from a single crystal once the driving frequency matches the characteristic frequency of the transducer[26,27], making the dual- or multiple-frequency US irradiation more feasible and bring opportunity for biomedical application such as transdermal drug delivery (TDD) enhancements
The stable cavitation dose (SCD) values during dual-frequency sonication were 1016.18 ± 172.13, 468.03 ± 66.55, and 323.63 ± 88.07 mV2·s/Hz in groups MB1, MB10, and MB20, respectively; the corresponding inertial cavitation dose (ICD) values were 3426.92 ± 554.95, 2062.21 ± 266.54, and 989.01 ± 296.50 mV2·s/Hz. Both SCD and ICD during dual-frequency US sonication were correlated with the MB concentration
Summary
Ultrasound (US) has been found to rejuvenate and invigorate the hair follicles, increase the size of hair shafts, and promote new hair growth. Our present study found that dual-frequency US-mediated microbubble (MB) cavitation significantly enhanced minoxidil (Mx) delivery in both in vitro and in vivo models, while increasing the hair growth efficacy compared to single-frequency US sonication. Our previous studies demonstrated that combined treatment with US using optimal parameters and optimal conditions (size or concentration) of microbubbles (MBs) can increase skin permeability so as to enhance drug delivery without increasing temperatures or causing heating damage[15,16]. Our previous study demonstrated that dual- or multiple-frequency US wave irradiations are possible to be generated from a single crystal once the driving frequency matches the characteristic frequency of the transducer[26,27], making the dual- or multiple-frequency US irradiation more feasible and bring opportunity for biomedical application such as transdermal drug delivery (TDD) enhancements.
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