Hyperbranched Macromonomer‐Based Gelation of Hyaluronic Acid for Efficient Liposome Encapsulation and Improved Transdermal Delivery

Liposome-based formulations, while facilitating drug penetration across physiological barriers, face considerable challenges, including instability, rapid clearance in vivo, and inadequate control over drug release. Incorporating liposomes into hydrogels presents a promising approach to enhancing stability and sustaining drug delivery. However, optimizing their administration, responsiveness, and synergistic interaction with the tissue penetration process to improve drug permeation efficiency and bioavailability remains a critical challenge. To address these limitations, this study introduces an intelligent, injectable hydrogel delivery system based on the crosslinking of thiolated hyaluronic acid with a versatile hyperbranched PEG macromer (HPM). The high reactivity and acid-responsive properties of HPM enable in situ, rapid liposome encapsulation, significantly enhancing liposome stability while ensuring excellent injectability and localized therapeutic effects. As a proof of concept, this hydrogel system is applied as a skin dressing, facilitating controlled liposome release while improving stratum corneum hydration, thereby markedly enhancing the transdermal delivery of the antioxidant coenzyme Q10 (CoQ10). Compared to the direct application of free CoQ10 dispersions, this system achieves an impressive 16.6-fold increase in bioavailability, highlighting its strong potential for applications in transdermal drug delivery and localized disease treatment.