Acne vulgaris affects a large proportion of adolescents and young adults and can lead to long-term scarring and psychological distress. Its pathogenesis involves excessive sebum production, bacterial proliferation, and inflammatory responses, making combination therapy a clinical necessity. Conventional topical formulations struggle to penetrate the stratum corneum, particularly for hydrophobic or high–molecular weight drugs, while oral treatments and physical therapies may cause systemic side effects or poor adherence. Although dissolving microneedles offer a promising transdermal alternative, most are limited to water-soluble drugs, restricting their use in combination therapy. Based on these challenges, there is a need to develop advanced delivery platforms capable of co-delivering hydrophilic and hydrophobic drugs effectively for acne treatment.
Researchers from Tsinghua Shenzhen International Graduate School and collaborating institutions report a new microneedle-based strategy for acne therapy in a study published (DOI: 10.1038/s41378-025-01079-y) in Microsystems & Nanoengineering on November 24, 2025. The team developed dissolved bubble microneedle patches that can simultaneously deliver hydrophilic and hydrophobic drugs directly into acne-affected skin. By integrating hollow bubble structures within dissolving microneedles, the platform enables spatially controlled drug loading and time-dependent release. In animal models, the system significantly reduced inflammation and bacterial burden compared with conventional topical treatments, highlighting its potential for improved acne management.
The newly developed dissolved bubble microneedle patches are fabricated from hyaluronic acid and feature microscale hollow bubbles embedded within each needle. This unique architecture allows different drugs to be loaded into distinct regions of the microneedle: a hydrophilic anti-inflammatory agent in the main body, a hydrophobic antibacterial compound within the bubble walls, and a keratolytic agent in the base layer. Microscopy and fluorescence imaging confirmed precise spatial separation of the three drugs, enabling sequential release after skin insertion.
Mechanical testing showed that the microneedles possess sufficient strength to penetrate the skin without fracture, achieving insertion depths of approximately 350 μm. Once inserted, the needles dissolve rapidly, releasing drugs locally while leaving no sharp waste. In vitro release studies revealed fast release of the keratolytic agent, sustained release of the hydrophobic antibacterial drug, and near-zero-order release of the anti-inflammatory compound, matching therapeutic needs in acne lesions.
In a mouse model of acne induced by bacterial injection, treatment with the drug-loaded microneedle patches led to a marked reduction in swelling, bacterial load, and pro-inflammatory cytokines, alongside increased anti-inflammatory signaling. Histological analysis further showed reduced inflammatory cell infiltration and preserved skin structure, demonstrating superior therapeutic outcomes compared with topical drug solutions or drug-free microneedles.
“This work addresses one of the most persistent challenges in acne therapy—how to deliver multiple drugs with very different properties to the same skin site,” said the study’s corresponding author. “By introducing bubble structures into dissolving microneedles, we created dedicated compartments for hydrophobic and hydrophilic agents without compromising mechanical strength or biocompatibility. The resulting sequential release profile closely matches the biological needs of acne lesions, offering rapid symptom relief together with sustained antibacterial action. This platform could be readily adapted for other inflammatory or infectious skin diseases.”
The dissolved bubble microneedle platform offers an efficient approach for acne therapy, combining minimally invasive administration with local drug delivery. Its complete dissolution eliminates sharps waste and improves patient safety and compliance, while the use of low-cost, biocompatible materials supports scalable manufacturing. Beyond acne vulgaris, the strategy may be extended to other dermatological conditions that require co-delivery of drugs with contrasting solubilities, such as chronic infections or inflammatory skin disorders. By overcoming fundamental formulation and penetration barriers, this work points toward a new generation of smart transdermal delivery systems with broad therapeutic potential.
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References
DOI
10.1038/s41378-025-01079-y
Original Source URL
https://doi.org/10.1038/s41378-025-01079-y
Funding Information
The authors greatly acknowledge the Key Research and Development Program of the Ministry of Science and Technology [2023YFA0914300 (2023YFA0914304)], fund from Shanghai Jahwa United Co., Ltd., National Natural Science Foundation of China (22278242), Guangdong Innovative and Entrepreneurial Research Team Program (2023ZT10C040), Shenzhen Technology and Innovation Commission (KCXFZ20230731094459001, KCXFZ20240903093102004), Shenzhen International Graduate School at Tsinghua University (HW2023009, JC2021011).
About Microsystems & Nanoengineering
Microsystems & Nanoengineering is an online-only, open access international journal devoted to publishing original research results and reviews on all aspects of Micro and Nano Electro Mechanical Systems from fundamental to applied research. The journal is published by Springer Nature in partnership with the Aerospace Information Research Institute, Chinese Academy of Sciences, supported by the State Key Laboratory of Transducer Technology.