Woman with acne spots pimple on face

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In A Nutshell

  • Dissolving microneedle patches embedded with microscopic bubbles deliver three acne medications simultaneously, solving the decades-old problem that water-loving and oil-loving drugs don’t mix in traditional formulations
  • Each 500-micrometer needle dissolves completely in two minutes, and the microscopic puncture sites become invisible within five minutes of removal with no visible marks or lasting irritation
  • The painless needles penetrate deep enough to bypass the skin’s protective barrier but stay too short to reach most pain-sensing nerve endings
  • In mouse studies, the patches eliminated acne bacteria and reduced inflammation more effectively than applying the same drugs as topical creams, which couldn’t penetrate deeply enough to reach infection sites

A patch covered in tiny needles sits on the skin for 120 seconds, then disappears. Five minutes later, even the microscopic holes it created become invisible. But within the dermis, three different medications are already at work killing bacteria and calming inflammation. Sounds too good to be true, but intriguing research now suggests such applications could be a future acne treatment.

Scientists at Tsinghua University engineered dissolving microneedle patches embedded with microscopic bubbles that solve a chemistry problem dermatologists have faced for decades: the most effective acne medications don’t mix. Water-loving antibiotics and oil-loving anti-inflammatory drugs separate in creams and gels, forcing patients to layer multiple products on their skin with limited success. The new patches deliver three incompatible drugs simultaneously by trapping oily medications inside hollow bubbles while the surrounding needle material carries water-soluble compounds.

Each needle measures just 500 micrometers tall: half a millimeter, about the thickness of five sheets of paper stacked together. That’s too short to reach most pain-sensing nerve endings, but long enough to punch through the stratum corneum, the tough outer layer that blocks most topical treatments. Standard acne creams and lotions barely penetrate this barrier, leaving the sebaceous glands where Propionibacterium acnes bacteria thrive largely untouched. The patches bypass that obstacle entirely, dissolving after insertion to deposit medication directly at infection sites. In mice with acne-like infections, they nearly eliminated bacteria more effectively than applying the same drugs topically and reduced ear swelling by more than half within three days.

How Bubble Microneedle Patches Deliver Multiple Acne Drugs

Creating needles that could carry both hydrophilic and hydrophobic drugs together required engineering at the microscopic scale. Researchers built the patches from hyaluronic acid, a sugar molecule already approved for cosmetic and medical uses. They cast the needle shapes in silicone molds through a two-step process. First, they poured hyaluronic acid mixed with dipotassium glycyrrhizinate (DPG) (an anti-inflammatory compound) into pyramid-shaped cavities and applied vacuum to remove air bubbles and help the liquid fill the tiny spaces.

The study, published in Microsystems & Nanoengineering, added droplets of PIONIN, an antimicrobial agent, dissolved in ethanol. Under vacuum conditions, the alcohol evaporated rapidly, leaving behind hollow bubble cavities roughly 176 micrometers wide with walls about 10 micrometers thick. The oily PIONIN became trapped in these bubble walls while the water-soluble DPG remained in the solid hyaluronic acid matrix surrounding them.

A third drug, salicylic acid, went into the base layer connecting the needles to their backing patch. When researchers labeled each drug with a different fluorescent dye and scanned the needles layer by layer with confocal microscopy, they confirmed the three compounds stayed in their designated compartments without mixing. DPG occupied the main needle body from tip to base, PIONIN concentrated in the bubble walls, and salicylic acid filled the foundation layer. The spatial separation meant incompatible drugs could travel together into skin without interacting or degrading each other.

The needles needed to thread a narrow engineering challenge: strong enough to puncture tough skin without breaking, yet short enough to avoid the nerve endings that register pain. Testing the mechanical properties of individual needles proved essential. Researchers used a microparticle strength tester to compress 50 randomly selected needles from their 10×10 arrays. Each needle withstood an average stress of 4.7 megapascals before bending (but not snapping), with a Young’s modulus of 144.8 megapascals, well above the force required to penetrate human skin.

When pressed into pig skin samples, the needles consistently reached depths around 350 micrometers. That’s deep enough to access the dermis where acne inflammation occurs but shallow enough that the tips stop before reaching the deeper nerve fibers responsible for pain sensation. Pain receptors typically sit roughly 1-2 millimeters below the skin surface. At half a millimeter tall, these needles fall well short of that depth, suggesting minimal discomfort during application.

The rapid dissolution surprised even the researchers. Within 120 seconds of insertion into pig skin, the needles melted away almost completely, releasing their drug payload. Optical microscopy showed the sharp pyramid tips and hollow bubble structures at the zero-second mark maintained their shape perfectly. By 30 seconds, the tips had begun to blur. At 60 seconds, roughly half the needle height remained. By 120 seconds, only faint remnants persisted. The micropores created by insertion became nearly invisible to the naked eye within five minutes after patch removal, and the surrounding skin showed no redness or swelling.

The spatial separation of medications inside the needles created something else valuable: temporal control over when each drug released. Once inserted, the three medications followed distinct schedules matched to their therapeutic purposes.

Salicylic acid burst out first. Over 50% released within 30 minutes and 95% by six hours. This rapid release helps unclog pores and reduce initial inflammation quickly, which matters for a drug working at the skin surface. DPG, embedded throughout the dissolving hyaluronic acid matrix, came out more steadily at a near-constant rate for the first four hours, reaching 70% release by six hours. This extended release maintains anti-inflammatory action as the needles dissolve progressively from tip to base.

PIONIN emerged slowest because of its poor water solubility, achieving only 50% release by the six-hour mark. But this sluggish release actually benefits treatment by prolonging antimicrobial action against P. acnes bacteria deep in sebaceous glands. The bacteria multiply in those oil-rich pockets, so having an oil-soluble drug present for longer periods increases the chances of eliminating the infection completely.

Safety testing with mouse fibroblast cells showed the dissolved needle material didn’t harm cells even at concentrations up to 800 micrograms per milliliter, where cell viability stayed above 80%. The patches killed acne bacteria effectively in laboratory dishes, producing clear zones where no bacteria grew on agar plates. Scanning electron microscopy revealed bacterial cells exposed to drug-loaded patches suffered severe damage: collapsed membranes and leaked cellular contents. Blank patches without drugs showed limited antibacterial activity, confirming that medications rather than physical effects did the work.

acne bubbles
Schematic illustration of DBMNPs for acne treatment. (DBMNPs: dissolved bubble microneedle patches, HA: hyaluronic acid, SA: Salicylic acid, DPG: Dipotassium glycyrrhizinate). Credit: Microsystems & Nanoengineering)

Microneedle Acne Treatment Outperforms Topical Creams in Animal Testing

For the animal study, researchers injected P. acnes bacteria into the right ears of mice to create acne-like infections, then divided the animals into five groups. One group received no treatment, another got blank patches without drugs, a third had drugs applied topically as a solution, and the final two groups served as healthy controls or received the drug-loaded bubble patches. Treatments happened once daily for three consecutive days.

Mice treated with drug-loaded bubble patches showed dramatically less redness and swelling than other groups by day three. Their ear thickness dropped from 0.6 millimeters back toward the normal 0.2 millimeters. Mice receiving drugs as topical solutions showed minimal improvement despite the solution having identical antimicrobial power in laboratory tests. The solution simply couldn’t penetrate deeply enough to reach infected tissue. The stratum corneum acts like a molecular bouncer, keeping out anything with a molecular weight above 500 Daltons or poor fat-solubility characteristics. All three drugs in this study exceed that threshold or have the wrong solubility profile.

This explains why many acne patients abandon their prescribed creams. The medications work perfectly when tested against bacteria in petri dishes, but those bacteria sit exposed to the drugs. On human skin, the bacteria hide in sebaceous glands buried beneath multiple layers of dead skin cells and living tissue. Topical applications might affect surface bacteria, but the deeper populations survive and multiply. The needles eliminate that problem by delivering drugs directly to the infection site.

Measurements of inflammatory markers reinforced these observations. The drug-loaded patches significantly reduced levels of interleukin-6, a molecule that promotes inflammation, while increasing interleukin-10, which fights inflammation. Tissue samples examined under microscopes showed nearly complete elimination of P. acnes bacteria in the patch-treated group, with minimal inflammatory cell infiltration and well-preserved skin structure. Untreated and solution-treated animals displayed extensive neutrophil infiltration characteristic of active infection.

Interestingly, even blank patches without medication provided modest benefits, possibly by increasing oxygen exposure to swollen tissue. P. acnes bacteria thrive in low-oxygen environments, so researchers hypothesize that the temporary channels created by the needles may have improved oxygen flow and inhibited bacterial growth. However, this effect was minor compared to drug-loaded patches.

Manufacturing and Market Potential

The materials and manufacturing methods position these patches closer to market entry than many experimental treatments. Hyaluronic acid, the main structural component, already has widespread approval for cosmetic and medical uses. Several companies sell dissolving microneedle patches for skincare, primarily targeting wrinkles or skin brightening. Those existing products contain only hydrophilic ingredients, limiting their therapeutic range. Adding the bubble structure expands what dissolving patches can deliver using materials already common in cosmetic and medical products, which could simplify clinical translation.

Manufacturing uses straightforward methods. Researchers poured drug-containing solutions into silicone molds shaped like arrays of tiny pyramids, applied vacuum to remove air bubbles and help material fill the molds, then added the oily drug solution to create bubbles before casting the base layer. After drying at room temperature (no heat, no complex equipment) they peeled finished patches off the molds. Each patch measured 1.5 centimeters in diameter and contained 100 needles arranged in a 10×10 grid. The entire fabrication process happens at room temperature with inexpensive materials, making mass production feasible.

For patients, the appeal is obvious. Apply a patch, wait two minutes, remove it, and the treatment is done. No visible marks remain. No lingering medication sitting on the skin surface that might transfer to pillowcases or other people. No need to remember multiple applications throughout the day or coordinate different products. The patch dissolves, the micropores close, and life continues. When tested on healthy mouse ears, the insertion sites became virtually invisible within five minutes, with no redness or swelling.

Woman looking in mirror, cleaning face, acne
In mouse studies, the patches proved more effective against acne bacteria than applying the same drugs as topical creams. (Andrea Piacquadio / pexels.com)

Unanswered Questions

Mouse ears aren’t human faces. The mouse ear model, while useful for initial testing, lacks the complex sebaceous gland structure found in human facial skin. Mice don’t naturally develop acne, so researchers had to inject bacteria rather than letting them colonize naturally. Human clinical trials will be essential to confirm whether the patches work as well on real acne patients as they did on experimentally infected mice.

Researchers noted they’re working to improve bubble formation consistency during manufacturing. Currently, bubble sizes vary somewhat, which could affect how much oily drug each needle delivers. Better control over bubble dimensions would ensure consistent dosing from needle to needle and patch to patch. They also plan to test the patches on other skin conditions that might benefit from combined hydrophilic and hydrophobic drug delivery, such as eczema or psoriasis.

The study tested three specific drugs but didn’t explore whether other medications could substitute. Different oily drugs might not form bubbles as reliably or might interact with hyaluronic acid in unexpected ways. The patches delivered fixed amounts of each medication, with no ability to adjust ratios for individual patients who might need more antibacterial versus anti-inflammatory treatment.

Long-term effects remain unexplored. The mouse study lasted only three days, leaving questions about whether repeated applications over weeks or months might cause skin irritation or diminishing effectiveness. Human acne treatment typically continues for months. Researchers checked for immediate skin reactions and found micropores healed quickly with no redness or swelling, but chronic use could reveal different issues. The patches also don’t address whether bacteria might develop resistance to the antibiotics after extended exposure, though the combination of three different mechanisms (antimicrobial, anti-inflammatory, and keratolytic) might reduce that risk.


Disclaimer: This article describes early-stage research conducted in laboratory settings and animal models. The dissolving microneedle patches discussed have not been tested in human clinical trials and are not currently available for consumer use. This content is for informational purposes only and should not be considered medical advice. Readers with acne or other skin conditions should consult qualified healthcare providers for diagnosis and treatment recommendations. The safety and effectiveness of these patches in humans have not been established.


Paper Notes

Study Limitations

Researchers acknowledged several constraints in their experimental design. The mouse model used ear infections rather than spontaneous acne formation, potentially affecting how well results translate to human facial acne. Sample sizes remained small, with only three mice per experimental group. The study duration of three days is insufficient to assess long-term effects or potential antibiotic resistance development. Bubble formation during manufacturing showed some variability, and investigators noted ongoing work to improve consistency. The research didn’t explore alternative drug combinations or test whether the platform could accommodate different oily medications beyond PIONIN.

Funding and Disclosures

This work received financial support from the Key Research and Development Program of the Ministry of Science and Technology (2023YFA0914300, specifically 2023YFA0914304), Shanghai Jahwa United Co., Ltd., the National Natural Science Foundation of China (grant 22278242), Guangdong Innovative and Entrepreneurial Research Team Program (2023ZT10C040), and Shenzhen Technology and Innovation Commission (KCXFZ20230731094459001, KCXFZ20240903093102004). Additional funding came from Shenzhen International Graduate School at Tsinghua University (HW2023009, JC2021011). The authors declared no competing interests.

Publication Details

Authors: Xiaopeng Zhang, Xiaotong Zhao, Yiting Li, Wanyue Zhang, Yuanyuan Chen, Haidong Jia, Zhibing Zhang, and Can Yang Zhang | Affiliations: Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, China; Key Laboratory of Bioactive Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes; Shanghai Jahwa United Co., Ltd.; School of Chemical Engineering, University of Birmingham, UK | Journal: Microsystems & Nanoengineering | Publication Date: November 24, 2025 (online) | Volume/Issue: Volume 11, Article 223 | DOI: https://doi.org/10.1038/s41378-025-01079-y | Article Type: Open Access | License: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License | Corresponding Author: Can Yang Zhang (zhang.cy@sz.tsinghua.edu.cn)

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