Minoxidil-Coated Lysozyme-Shelled Microbubbes Combined With Ultrasound for the Enhancement of Hair Follicle Growth: Efficacy In Vitro and In Vivo

Abstract

Lysozyme (Lyz) is an antimicrobial peptide, a safe adjunct, and it has been indicated that Lyz can promote vibrissae follicle growth by enhancing the hair-inductive capacity of dermal papilla cells in mice. The present study produced a new type of minoxidil (Mx)-coated antifungal Lyz-shelled microbubble (LyzMB) for inhibiting bacteria and allergies on the oily scalp. The potential of Mx-coated LyzMBs (Mx-LyzMBs) combined with ultrasound (US) and the role of LyzMB fragments in enhancing hair follicle growth were investigated. Mx grafted with LyzMBs were synthesized and the loading efficiency of Mx on cationic LyzMBs was 20.3%. The biological activity of Lyz in skin was determined using an activity assay kit and immunohistochemistry expression, and the activities in the US+Mx-LyzMBs group were 65.8 and 118.5 μU/mL at 6 and 18 h, respectively. In hair follicle cell culture experiments, the lengths of hair follicle cells were significantly enhanced in the US+Mx-LyzMBs group (108.2 ± 11.6 μm) compared to in the US+LyzMBs+Mx group (44.3 ± 9.8 μm) and the group with Mx alone (79.6 ± 12.0 μm) on day 2 (p < 0.001). During 21 days of treatment in animal experiments, the growth rates at days 10 and 14 in the US+Mx-LyzMBs group increased by 19.4 and 65.7%, respectively, and there were significant differences (p < 0.05) between the US+Mx-LyzMBs group and the other four groups. These findings indicate that 1-MHz US (applied at 3 W/cm2, acoustic pressure = 0.266 MPa) for 1 min combined with Mx-LyzMBs can significantly increase more penetration of Mx and LyzMB fragments into skin and enhance hair growth than Mx alone.

Making waves: how ultrasound-targeted drug delivery is changing pharmaceutical approaches

“…127,128 In another application, lysozyme-shelled microbubbles carrying minoxidil combined with insonation (1 MHz, 3 W cm À2 , 0.266 MPa) enhanced hair follicle growth in a mouse model. 129 They demonstrated approximately 66% increased hair follicle growth rates using the minoxidil-loaded lysozyme microbubbles with ultrasound, which was significant compared to control groups. 129 Similarly, Liao et al used ultrasound-sensitive lysozyme-shelled microbubbles to deliver adapalene to a mouse model of photoaging skin, resulting in significant wrinkle reduction with in the mice treated with this UTDD agent and insonation (1 MHz, 3 W cm À2 for 1 minute).…”

“…129 They demonstrated approximately 66% increased hair follicle growth rates using the minoxidil-loaded lysozyme microbubbles with ultrasound, which was significant compared to control groups. 129 Similarly, Liao et al used ultrasound-sensitive lysozyme-shelled microbubbles to deliver adapalene to a mouse model of photoaging skin, resulting in significant wrinkle reduction with in the mice treated with this UTDD agent and insonation (1 MHz, 3 W cm À2 for 1 minute). 130 Microbubbles and ultrasound have also been investigated for applications in drug delivery to the eye, including temporary disruption of the blood-retina barrier, increased cellular uptake, and targeted delivery.…”

Innovative Strategies for Hair Regrowth and Skin Visualization

“…Leveraging the cavitation effect induced by ultrasound, researchers designed MXD (Mx)-coated lysozyme-shelled microbubbles (LyzMBs). The mice treated with Mx-LyzMBs combined with ultrasound were found to have significantly longer hair shafts [58]. In addition to drug delivery, ultrasound can also increase the permeation of proteins.…”

Does topical minoxidil at concentrations higher than 5% provide additional clinical benefit?

“…6 Microbubbles are shelled with lysozymes, which are anti-infective, and these are then subsequently coated with minoxidil; the resultant compound is then combined with ultrasound waves to guide its delivery precisely into the hair follicle for better results. 7…”

“…Newer technology‐based formulations, including nanotechnology, have helped form minoxidil formulations loaded on lipid, polymer or inorganic compounds 6 . Microbubbles are shelled with lysozymes, which are anti‐infective, and these are then subsequently coated with minoxidil; the resultant compound is then combined with ultrasound waves to guide its delivery precisely into the hair follicle for better results 7 …”