Living Bacterial Microneedles for Fungal Infection Treatment

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.

Living Bacterial Hydrogels for Accelerated Infected Wound Healing

“…[ 28 ] Furthermore, Bacillus subtilis has been employed as a producer of antifungal agents for treating fungal infections. [ 29 , 30 ] However, the application of bacteria has been largely limited due to the intrinsic nature of bacteria, including rapid proliferation and colonization, which may result in uncontrollable invasion. [ 31 , 32 ] In addition, exposed bacteria often cause attacks by the immune system and cannot achieve desired therapeutic effects.…”

Microneedle arrays integrated with living organisms for smart biomedical applications

“…For example, considering the competition between beneficial bacteria and other microbes, Zhao et al . proposed a hydrogel-forming MNA that encapsulates living B. subtilis to secrete anti-fungal lipopeptides against C. albicans infection ( Figure 5 B ) 82 . The beneficial bacteria were long-term maintained inside the MNAs and therefore would not cause an undesirable immune response, indicating a safe treatment.…”

“…(iii) These MNAs showed effective capability when treating fungi-infected skin similar to ketoconazole. Reproduced with permission from American Association for the Advancement of Science 2020 82 .…”

Versatile Ice Microneedles for Transdermal Delivery of Diverse Actives

“…[ 21 , 22 ] Benefitting from these outstanding properties, microneedles have been widely applied to the release of various actives, including small molecule drugs, proteins, and vaccines. [ 23 , 24 , 25 , 26 , 27 , 28 ] However, to achieve successful penetration, the materials of microneedles should satisfy the strength and hardness requirements, which impose great limitations on the choices of their components and thus restrict the applications of microneedles. In addition, many actives are very demanding on the surrounding environments and each has different requirements for loading conditions, while there are no such microneedles that are broadly applicable to the carriage and delivery of almost all actives, including the vulnerable or cell‐related ones.…”