Schematic illustration of the 1 × 1 cm microneedle patch for the treatment of acne. (Credit: University of Hong Kong)

A research team has designed a new microneedle patch to offer a highly effective nonantibiotic approach for the treatment of skin infection. In brief, the design engineered with ultrasound-responsive zinc-based metal-organic framework (MOF) antibacterial nanoparticles promises pain-free delivery to treat bacterial infection on skin tissue and facilitate skin repair at the same time. The team was led by Prof. Kelvin Yeung Wai-kwok, department of orthopaedics and traumatology, School of Clinical Medicine, LKS Faculty of Medicine, University of Hong Kong (HKUMed). The novel microneedle is around 50 μm in diameter, similar to a typical hair. The findings have been published in Science Advances.

Background

Acne is a common skin disease worldwide that affects more than 80 percent of teenagers and young adults.1 The primary cause can be attributed to excessive lipid secretion that clogs the hair follicles, thereby establishing a hypoxic microenvironment in skin tissue. This undesirable condition particularly favors to the proliferation of Propionibacterium acnes (P. acnes) bacteria. Infected pimples, regarded as one of the skin infections, is mainly caused by P. acnes bacteria, which affects millions of people worldwide. It not only causes the patients with significant physical and emotional distress but may also develop into chronic inflammatory condition without proper treatment. The clinical management normally includes nonprescription treatment (i.e., benzoyl peroxide and salicylic acid), or the administration of antibiotics orally or topically. However, such treatments can be ineffective or have unpleasant side effects.

Treatment of acne through efficient ultrasound-triggered antibacterial nanoparticles embedded microneedle patch. (Credit: University of Hong Kong)

In general, the first-line treatment for an infected pimple is antibiotics administered either oral or topical. However, the therapeutic effect of topical antibiotic treatment is concerning, particularly when the drugs pass through the skin tissue. Also, the treatment becomes less effective when bacteria are drug resistant or when they migrate to subcutaneous tissue. In addition, P. acnes bacteria can secrete extracellular polysaccharides to form biofilm that blocks out the attacks initiated by antibacterial agents or immune cells.

Most microneedle products on the market mainly use pharmaceutical ingredients to treat acne. However, repeated applications of antibiotics may reduce the sensitivity of bacteria to drugs. Patients who have been affected by acne for a long time know that the beneficial effects of the same treatment products can be significantly reduced after long-term use.

Research Method and Findings

The microneedle patch facilitates the transdermal delivery of ultrasound-responsive antibacterial nanoparticles to treat the infection induced by P. acnes using a minimally invasive approach. In the current design, ultrasound-responsive antibacterial nanomaterials are introduced to the microneedle patch, which responds to bacterial infection quickly and efficiently. The use of drugs is avoided in the treatment of acne.

The modified nanoparticles comprised of ZnTCPP and ZnO can produce a substantial amount of reactive oxygen species (ROS) subject to ultrasound stimulation, which can effectively oxidize the key cellular macromolecules of bacteria. The results demonstrate that the killing of P. acnes bacteria mediated by ROS can reach to 99.73 percent after 15 minutes of ultrasound stimulation. Also, the levels of inflammatory markers, including tumor necrosis factor-a (TNF-α), interleukins (ILs), and matrix metallo-proteinases (MMPs) are significantly reduced. Furthermore, the zinc ions released can elevate the DNA replication-related genes, thereby augmenting more fibroblasts toward superior skin repair.

Research Significance

“The new microneedle patch enabling ROS generation upon ultrasound stimulation, regarding as a nonantibiotic and transdermal approach, can not only effectively address the infection induced by P. acnes bacteria, but also facilitates the skin repair due to zinc ion release,” says Prof. Wai-kwok. “Due to the specific killing mechanism of ROS, we believe that this design is also able to address other skin infections induced by fungi, parasites, or viruses, such as tinea pedis (known commonly as Athlete’s Foot or Hong Kong Foot).”

This research study was led by Prof. Yeung. The first author, Xiang Yiming, is the PhD candidate under Prof. Yeung’s supervision.

This work was jointly supported by the National Key R&D Programmes of China (2018YFA0703100), the General Research Fund of Hong Kong Research Grants Council (Nos. 17207719 and 17214516), the Health Bureau Health and Medical Research Fund (Nos.19180712,20190422and21200592), the Innovation and Technology Fund Partnership Research Programme (PRP/030/30FX), the National Science Fund for Distinguished Youth Scholars (No. 51925104), Shenzhen Science and Technology Programme (Nos. JSGG20180507183242702 and JCYJ20210324120009026), and the Shenzhen’s Sanming Project of Medicine – ‘Team of Excellence in Spinal Deformities and Spinal Degeneration’ (SZSM201612055).

Reference

  1. Lee, Y.B.; Byun, E.J.; Kim, H.S. Potential Role of the Microbiome in Acne: A Comprehensive Review. Journal of Clinical Medicine, Vol8(7), pp 987, June 2019.

For more information, contact Prof. Kelvin Yeung Wai-kwok via e-mail at This email address is being protected from spambots. You need JavaScript enabled to view it. or visit here  .

Read the full scientific paper below.

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Ultrasound-triggered Interfacial Engineering-based Microneedle for Bacterial Infection Acne Treatment

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    Overview

    The document presents a research study focused on an innovative approach to treating acne through the use of ultrasound-triggered microneedles. The study introduces a sodium hyaluronate microneedle patch that incorporates ultrasound-responsive nanoparticles designed to target and eliminate the bacteria responsible for acne, specifically Propionibacterium acnes.

    The research highlights the increasing prevalence of acne, which affects a significant portion of the population, particularly adolescents and young adults. Traditional treatments often involve antibiotics, which can lead to resistance and other side effects. This study aims to provide a more effective and safer alternative.

    The microneedle patch is engineered to deliver therapeutic agents directly into the skin while utilizing ultrasound stimulation to enhance its antibacterial efficacy. The results demonstrate an impressive antibacterial efficiency of 99.73% against P. acnes when subjected to ultrasound irradiation. This high level of effectiveness suggests that the method could significantly reduce bacterial load and inflammation associated with acne.

    In addition to its antibacterial properties, the microneedle patch promotes skin repair and healing. The study outlines the experimental protocols used to assess the patch's performance, including in vitro cell culture experiments and assessments of cell viability and morphology. The researchers employed advanced techniques such as transcriptome sequencing and quantitative reverse transcription PCR (qRT-PCR) to analyze gene expression related to skin healing and inflammation.

    The findings indicate that the ultrasound-triggered microneedle patch not only effectively targets acne-causing bacteria but also supports the skin's natural healing processes. This dual action could lead to improved outcomes for individuals suffering from acne, reducing the need for systemic antibiotics and minimizing potential side effects.

    The document concludes by acknowledging the collaborative efforts of the research team and the funding sources that supported the study. The authors express optimism about the potential of this innovative treatment strategy to revolutionize acne management and improve the quality of life for those affected by this common skin condition.

    Overall, this research represents a significant advancement in dermatological treatments, combining nanotechnology and ultrasound to create a targeted, effective, and safe solution for acne treatment.