Formulation approaches and strategies for transdermal delivery of insulin: special emphasis on microneedle-based systems

The prevalence of diabetes is increasing and expected to become a major global health burden. Various pharmaceutical approaches have been used to manage diabetes and reduce the associated risks. Subcutaneous insulin injection remains the primary treatment due to the physicochemical properties of insulin, which limit oral absorption. The gastrointestinal tract presents further challenges, including enzymatic degradation and harsh environmental conditions, resulting in oral insulin bioavailability < 1%. As a result, alternative delivery routes, such as transdermal delivery, have been extensively explored. However, this approach is also challenging due to the structural barriers of the skin, which hinder drug absorption. The high molecular weight of insulin further limits permeation across the skin. To address these limitations, various formulation and delivery strategies have been investigated to improve transdermal drug delivery of insulin and are the subject of this review. Approaches, including penetration enhancers, lipid-based carriers, microemulsion, polymeric systems, and physical enhancement technologies, have demonstrated potential for enhancing skin permeability. However, the potential adverse effects and patient discomfort associated with these conventional methods highlights the need for more user-friendly alternatives. Microneedles have emerged as a promising transdermal delivery system, offering a painless, simple, and user-friendly approach to overcome challenges, thus improving adherence and treatment efficacy.