Treatment effects of lysozyme-shelled microbubbles and ultrasound in inflammatory skin disease

Abstract

Acne vulgaris is the most common skin disorder, and is caused by Propionibacterium acnes (P. acnes) and can induce inflammation. Antibiotic therapy often needs to be administered for long durations in acne therapy, which results in extensive antibiotic exposure. The present study investigated a new treatment model for evaluating the antibacterial effects of lysozyme (LY)-shelled microbubbles (MBs) and ultrasound (US)-mediated LY-shelled MBs cavitation against P. acnes both in vitro and in vivo, with the aims of reducing the dose and treatment duration and improving the prognosis of acne vulgaris. In terms of the in vitro treatment efficacy, the growth of P. acnes was inhibited by 86.08 ± 2.99% in the LY-shelled MBs group and by 57.74 ± 3.09% in the LY solution group. For US power densities of 1, 2, and 3 W/cm2 in the LY-shelled MBs group, the growth of P. acnes was inhibited by 95.79 ± 3.30%, 97.99 ± 1.16%, and 98.69 ± 1.13%, respectively. The in vivo results showed that the recovery rate on day 13 was higher in the US group with LY-shelled MBs (97.8 ± 19.8%) than in the LY-shelled MBs group (90.3 ± 23.3%). Our results show that combined treatments of US and LY-shelled MBs can significantly reduce the treatment duration and inhibit P.-acnes-induced inflammatory skin diseases.

Sonobactericide: An Emerging Treatment Strategy for Bacterial Infections

“…In addition to the antibiotics, three other antimicrobials were investigated: sodium hypochlorite (NaOCl), lysozyme and human b-defensin 3 ( Table 1). The studies included either clinically appropriate antimicrobials (dental, NaOCl [Halford et al 2012]) or antimicrobials testing a new approach (lysozyme [Liao et al 2017]; human b-defensin 3, [Zhu et al 2013, Li et al 2015, Zhou et al 2018). Sodium hypochlorite is a disinfectant used widely in endodontic irrigation and health care facilities (Estrela et al 2002).…”

“…Nylon membrane biofilms were treated in a beaker placed in a sonicator (0.042 MHz, on for 2 s every 2 min) while microbubbles were continuously introduced for 15 min (Agarwal et al 2014). The planktonic bacteria in tubes were treated (1 MHz, 500 W/cm 2 , 2% duty cycle) for 5 min (Vollmer et al 1998) or 12 h (0.0465 MHz, 0.01 W/cm 2 , 33% duty cycle) (Zhu et al 2014) and in Eppendorf tubes (1 MHz, 1À3 W/cm 2 , 50% duty cycle) for 1 min (Liao et al 2017), all with a one-time administration of microbubbles.…”

“…Three in vitro studies were followed up with a corresponding in vivo study in the same article (He et al 2011;Lin et al 2015;Liao et al 2017). Thirty percent of the articles on sonobactericide (8/27) have investigated therapeutic efficacy in pre-clinical animal models (Table 1).…”

“…Lavage and tissues samples were evaluated at 30 min and 2 h, respectively, after ultrasound application. Liao et al (2017) also used mice and aimed to improve acne vulgaris treatment using transdermal sonobactericide with lysozyme-shelled microbubbles. Ears were infected intradermally with Propionibacterium acnes.…”

“…The protein lysozyme was used as the drug and also formed the coating of microbubbles. One study custom-made these microbubbles with an air gas core (mean diameter of 4 § 1 or 6 § 2 mm, depending on the duration of protein denaturation: 15 and 2 min, respectively) (Cavalieri et al 2008;Zhou et al 2012), and another used C 3 F 8 (mean diameter: 2.5À2.9 mm, depending on the sonication power) (Liao et al 2017). Lysozyme-coated microbubbles loaded with either spherical bovine serum albumin-coated gold nanoparticles (4.5 nm in diameter) or polyvinylpyrrolidonecoated gold nanoparticles (15 nm in diameter) were also produced by Cavalieri et al (2013).…”