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

Yantao Zhang1,2 ,  Guirong Wang3 ,  Yan Zhou1,2*
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1 Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
2 Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
3 Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, United States of America
BMT 2025 , 6(3), 314–333; https://doi.org/10.12336/bmt.24.00045
Submitted: 26 July 2024 | Revised: 13 September 2024 | Accepted: 22 October 2024 | Published: 22 September 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

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.

Keywords
Microneedles
Musculoskeletal disorders
Natural polymers
Polysaccharides
Protein-based polymer
Transdermal drug delivery system
Funding
This work was funded by National Natural Science Foundation of China (Nos. 82272528, 81802203), and Natural Science Foundation of Hubei Province (No. 2022CFB117).
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