Associate Professor Ulsan National Institute of Science and Technology (UNIST), United States
Introduction:: Inflammatory skin disorders (ISD) are characterized by abnormal inflammatory responses in the skin. These diseases are marked by the activation of both innate and adaptive immune systems through the generation of inflammatory cytokines. Inflammatory skin conditions such as psoriasis and atopic dermatitis are characterized by excessive inflammation and severe itching that causes distress to patients. As a result, repeated scratching of the skin can exacerbate inflammation, leading to a vicious cycle that thickens and hardens the skin, making it difficult for medications to penetrate into the affected area. These inflammatory skin disorders are typically managed with topical corticosteroid creams or ointments, phototherapy, oral medications, or biologic agents. Typically, these inflammatory skin diseases are treated with topical steroids, creams, phototherapy, oral medications, or biologics. However, topical patches or creams have significant limitations in delivering drugs through the thickened skin due to inflammation, and direct injection into the skin can cause significant pain and even trauma. Microneedles are an attractive drug delivery method that can overcome these limitations. They have the ability to deliver drugs directly into the skin without requiring additional equipment. By encapsulating active ingredients into porous silicon microparticles, which are then incorporated into microneedles, the thick epidermal layer that causes low drug absorption in skin disorders can be penetrated, and sustained release of multiple drugs can be achieved through the porous structure of the microneedles, thereby maximizing therapeutic efficacy.
Materials and Methods:: Porous silicon microparticles were obtained in film form by creating pores through a silicon wafer using a current of approximately 20mA/cm2 and subsequently lift-off. Multiple layers of film were then produced and sonicated for approximately 30 minutes, resulting in microparticles with a pore size of around 20nm and a thickness of approximately 15μm. The inflammasome inhibitor MCC950 was loaded into the porous silicon pores using the trapping method with MgCl2. Microneedles were created by pouring polydimethylsiloxane (PDMS) onto a master structure and allowing it to cure overnight. Hyaluronic acid and drug-loaded microparticles that are non-toxic and quickly dissolve in vivo were then introduced into the PDMS mold and centrifuged to fill the solution and create the microneedles.
Results, Conclusions, and Discussions:: We produced porous silicon microparticles to encapsulate drugs, which have a higher surface area than other particles such as liposomes and can therefore encapsulate more drugs. These porous silicon microparticles are created through a series of processes including etching on a silicon wafer and sonication, allowing the pore size and particle size to be controlled at each step and enabling the production of porous silicon microparticles tailored to specific purposes. We loaded a small molecule (MCC950) that inhibits inflammasomes, which induce the maturation of inflammatory cytokines associated with the innate immune defense system, into the porous silicon microparticles for delivery. We confirmed that the drug was gradually released over time. Inflammatory skin such as psoriasis and atopic dermatitis have many limitations about delivering drugs via ointment due to the excessively thick epidermis. To deliver drugs to the epidermis and dermis, we produced microneedles. The microneedles, made from hyaluronic acid, quickly dissolve in vivo, allowing the drug-encapsulated porous silicon microparticles to be released and minimizing the inflammatory response to alleviate inflammatory skin conditions.
Inflammatory skin diseases, characterized by excessive stratification and stratum corneum, have shown diminishing therapeutic effects with topical application of immunosuppressive drugs. Therefore, new drug delivery methods are in demand, among which microneedle-based drug delivery has been reported as a noteworthy approach that effectively delivers drugs with minimal pain compared to injection, which can cause severe discomfort. One important factor in developing patches for treating skin diseases is to minimize irritation to the skin. Among various types of microneedles, dissolving microneedles were used to minimize skin irritation by delivering drugs within 10 minutes of insertion, after which the needle dissolves. Since most drugs used are hydrophobic, porous silicon microparticles were utilized due to the limitations of hydrophilic microneedles. These porous silicon microparticles have a larger surface area than liposomes or other polymer-based particles, allowing for more drug delivery and cost-effectiveness. Using these porous silicon microparticles, drugs that inhibit inflammasomes were delivered to suppress Th17, which causes inflammatory skin diseases such as psoriasis, and alleviate inflammation. This approach may pave the way for new treatments for inflammatory skin diseases.
