Therapeutic potential of natural polymer-based transdermal drug delivery system for musculoskeletal disorders.

The transdermal drug delivery system is a highly safe and well-tolerated therapeutic approach with significant potential for treating musculoskeletal disorders. However, its clinical application is limited by the low skin permeability of many active drugs in its formulations. To overcome this challenge, advancements in skin permeation enhancement techniques are essential. Over the past decade, natural polymers have been increasingly incorporated into various nanocarriers due to their availability, biodegradability, and biocompatibility, offering new options for the effective dispersion of suspended solids. Furthermore, surface functionalisation of the numerous functional groups found in natural polymers allows them to be transformed into targeted and stimulus-responsive materials, enabling precise drug delivery to musculoskeletal tissues. This review examines the mechanisms of action of natural polymer-based transdermal drug delivery system, covering penetration enhancers, nanoparticles, microneedles, hydrogels, and nanofibres derived from chitosan, hyaluronic acid, sodium alginate, cellulose, and proteins, and their applications in treating musculoskeletal disorders. Moreover, it outlines the current challenges and prospects of polymer-based transdermal drug delivery system for localised treatment, offering insights into current therapeutic approaches and proposing new directions for advancements in this field.