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<p>Microneedle patch (MNP) technology offers a promising strategy for effectively transdermal delivery of macromolecular agents for treating various diseases, in particularly, dissolvable MNPs containing liposomes with tunable physicochemical properties have received widespread attention for improving macromolecular therapeutic efficacy. However, their design and optimization remain challenging. In this work, a series of liposomes with different size and modulus (100 vs. 500&#xa0;nm, ~ 0.2 vs. ~ 100&#xa0;kPa) were prepared and then integrated with poly(<i>γ</i>-glutamic acid) (<i>γ</i>-PGA) to form dissolvable MNPs containing liposomes with good loading capacity, mechanical properties and biocompatibility via centrifugation-assisted micromolding for transdermal macromolecular delivery, and more uniformly dispersed liposomes appeared in the microneedle matrix for smaller liposomes (100&#xa0;nm). Using FITC-dextran as the model macromolecule loaded in liposomes (100&#xa0;nm) in PGA-based MNPs, in vitro and in vivo transdermal experiments revealed that MNPs containing liposomes were beneficial for improving macromolecular therapeutic efficacy, and low-modulus liposomes (~ 0.2&#xa0;kPa) delivered had a more pronounced effect on the extension of the retention duration and region of macromolecular cargo in skin than high-modulus liposomes (~ 100&#xa0;kPa) possibly due to their lower macrophage uptake and stronger diffusion ability. Our findings will be useful to guide the design and construction of MNP-based transdermal macromolecular composite-delivery systems.</p> Graphical abstract <p></p>

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Poly(γ-glutamic acid)-based microneedle patches containing modulus-tunable liposomes for improving transdermal delivery of macromolecular agents

  • 期刊论文

  • 发表日期：

    2026年7月21日

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  • Shuang Wu,
  • Xiaoyu Li,
  • Jiayi Xu,
  • Rong Zeng

摘要

Microneedle patch (MNP) technology offers a promising strategy for effectively transdermal delivery of macromolecular agents for treating various diseases, in particularly, dissolvable MNPs containing liposomes with tunable physicochemical properties have received widespread attention for improving macromolecular therapeutic efficacy. However, their design and optimization remain challenging. In this work, a series of liposomes with different size and modulus (100 vs. 500 nm, ~ 0.2 vs. ~ 100 kPa) were prepared and then integrated with poly(γ-glutamic acid) (γ-PGA) to form dissolvable MNPs containing liposomes with good loading capacity, mechanical properties and biocompatibility via centrifugation-assisted micromolding for transdermal macromolecular delivery, and more uniformly dispersed liposomes appeared in the microneedle matrix for smaller liposomes (100 nm). Using FITC-dextran as the model macromolecule loaded in liposomes (100 nm) in PGA-based MNPs, in vitro and in vivo transdermal experiments revealed that MNPs containing liposomes were beneficial for improving macromolecular therapeutic efficacy, and low-modulus liposomes (~ 0.2 kPa) delivered had a more pronounced effect on the extension of the retention duration and region of macromolecular cargo in skin than high-modulus liposomes (~ 100 kPa) possibly due to their lower macrophage uptake and stronger diffusion ability. Our findings will be useful to guide the design and construction of MNP-based transdermal macromolecular composite-delivery systems.

Graphical abstract