Abstract

Fungal infections are everlasting health challenges all over the world, bringing about great financial and medical burdens. Here, inspired by the natural competition law of beneficial bacteria against other microbes, we present novel living microneedles (LMNs) with functionalized bacteria encapsulation for efficient fungal infection treatment. The chosen beneficial bacterial components, Bacillus subtilis (B. subtilis), which are naturally found on the human skin and widely used for food processing, can get nutrients from the skin and escape from the immune system with the help of microneedles. Besides, the encapsulated B. subtilis can continuously produce and secrete various potential antifungal agents which can directly bind to fungal cell surface-associated proteins and destruct the cell membranes, thus avoiding drug resistance. After immobilization in the LMNs, the bacteria can stay within the LMNs without invasion and the encapsulated bacteria together with microneedles can be removed after application. Thus, the side effects, especially the risk for subsequent bacterial infections, are controlled to a minimum to ensure security. In addition, strong penetrability of the microneedles enhances penetration of antifungal agents, and their heights can be adjusted according to the infected depth to acquire better therapeutic effects. These features make the LMNs potentially valuable for clinical applications.

Highlights

  • Fungal infections, caused by various fungi such as dermatophytes, Candida sp, and Malassezia sp, may invade all kinds of tissues, organs, and implanted instruments in the human body and affect 20-25% of the population worldwide [1,2,3]

  • The porous microneedles were fabricated from an aqueous solution of biocompatible polymer poly diacrylate (PEGDA) and polyvinyl alcohol (PVA) via a micromolding approach

  • The crosslinked poly (ethylene glycol) diacrylate (PEGDA)-based matrix could enhance the stiffness of the microneedles for efficient penetration through the skin, as well as enable sustained release of antifungal agents from the microneedles for maintaining high local concentrations in pathological tissues

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Summary

Introduction

Fungal infections, caused by various fungi such as dermatophytes, Candida sp, and Malassezia sp, may invade all kinds of tissues, organs, and implanted instruments in the human body and affect 20-25% of the population worldwide [1,2,3]. The predominant bacteria can effectively repel, block, and interfere with other microbial reproduction and preempt living space through rapid, mass reproduction and colonization [21,22,23] During this process, they could secrete abundant antimicrobial agents to enhance competitiveness [24, 25]. By encapsulating a safe gram-positive bacteria Bacillus subtilis (B. subtilis) that are naturally found on the human skin and commercialized in the food industry, functional LMNs, which could efficiently produce and secrete a range of potential antifungal agents such as lipopeptides (LPs), directly extract fungal cell surface-associated proteins, destruct the cell walls, and kill the target fungi, were achieved. These features make the LMNs valuable in practical fungal infection treatment and promising for various disease treatments

Results
Discussion
Materials and Methods
Conflicts of Interest
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