Advancements in Transdermal Drug Delivery Systems: Harnessing the Potential of Macromolecular Assisted Permeation Enhancement and Novel Techniques

Transdermal drug delivery (TDD) represents a transformative paradigm in drug administration, offering advantages such as controlled drug release, enhanced patient adherence, and circumvention of hepatic first-pass metabolism. Despite these benefits, the inherent barrier function of the skin, primarily attributed to the stratum corneum, remains a significant impediment to the efficient permeation of therapeutic agents. Recent advancements have focused on macromolecular-assisted permeation enhancers, including carbohydrates, lipids, amino acids, nucleic acids, and cell-penetrating peptides, which modulate skin permeability by transiently altering its structural integrity. Concurrently, innovative methodologies such as iontophoresis, electroporation, microneedles, ultrasound, and sonophoresis have emerged as potent tools to enhance drug transport by creating transient microchannels or altering the skin's microenvironment. Among the novel approaches, the development of nanocarriers such as Liposome, niosomes, and transethosomes etc. has garnered substantial attention. These elastic vesicular systems, comprising lipids and edge activators, exhibit superior skin penetration owing to their deformability and enhanced payload delivery capabilities. Furthermore, the integration of nanocarriers with physical enhancement techniques demonstrates a synergistic potential, effectively addressing the limitations of conventional TDD systems. This comprehensive convergence of macromolecular-assisted enhancers, advanced physical techniques, and next-generation nanocarriers underscores the evolution of TDD, paving the way for optimized therapeutic outcomes.

Graphical Abstract