Nanocarriers and their integrated microneedle systems-mediated drug delivery for the treatment of moderate-severe dermatological diseases: Recent progress, applications and future perspectives

Abstract

Dermatological diseases significantly affect patients' quality of life and psychological well-being due to their visible symptoms. Currently, treatment options for these conditions include systemic medications, topical treatments, phototherapy, radiotherapy, chemotherapy, surgical resection, and injections. However, each of these treatments has its limitations. In this context, transdermal drug delivery (TDD) is particularly appealing because it allows for the delivery of drugs to affected tissues, reducing systemic side effects. Unfortunately, the stratum corneum (SC), the outermost layer of the skin, severely hampers drug permeation. Nanocarriers loaded with drugs could offer a promising solution for penetrating this SC barrier due to their small size, ideally less than 100 nm. These nanocarriers can also enhance the solubility, stability and target delivery efficiency of the encapsulated drugs. However, the thickened and highly keratinized skin still acts as a barrier to the permeation of these nanocarriers. To overcome this issue, microneedles (MNs) with micron-sized needles can pierce the SC, enabling drug delivery into the viable epidermis and dermis layers of the skin. Therefore, nanocarrier-integrated MN systems can significantly improve drug targeting while minimizing systemic drug exposure and related side effects. This review discusses the anatomy of the skin, the pathways for drug permeation, and methods to enhance drug delivery through the skin, including both chemical and physical approaches. It specifically focuses on various nanocarriers used in TDD and their application in treating moderate to severe dermatological diseases such as psoriasis, atopic dermatitis, and melanoma. It also examines the current therapies for these conditions, advancements in nanocarrier technologies, their integration with MN systems, and their potential applications, along with the challenges and future directions in this field.