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Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease
Open accessAbstract
Minocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra‐pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline‐loaded dissolvable microneedle (Mino‐DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two‐step casting micro‐molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino‐DMN patch features an array of minocycline‐enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino‐DMN inhibits pro‐inflammatory factors, promotes anti‐inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino‐DMN offers a simple, efficient, user‐friendly strategy for the adjunctive treatment of periodontal disease.
Overview
CoChat Summary
TL;DR
A minocycline-loaded dissolvable microneedle (Mino-DMN) patch with gelatin tips and a porous hyaluronic acid backing delivers minocycline locally to gingiva and shows antibacterial, anti-inflammatory, and bone-protective effects in a rat periodontitis model. It surpasses topical minocycline and is largely comparable to Periocline® ointment, though alveolar bone loss (ABL) was significantly higher in the Mino-DMN group than in the Periocline® group.
Key findings
- The two-step casting process concentrated minocycline in the microneedle tips: actual loading was 51 ± 6 μg per patch; a solid backing caused approximately three times greater drug loss than the porous backing, and sucrose-containing HA backing had a modulus approximately three times higher than pure HA backing.
- Microneedles sustained approximately 0.13 N per tip before fracturing, achieved 100% penetration in rat oral mucosa, and penetrated to approximately 120–200 μm; in vitro, more than 80% of Rhodamine 6G released within 5 min and complete release occurred at 30 min, while in vivo retention lasted up to 150 min versus negligible topical residue at 30 min.
- Against *Porphyromonas gingivalis*, Mino-DMN produced inhibition zones of 3.32 ± 0.26 cm at 2 days and 3.47 ± 0.31 cm at 7 days; no inhibition zones appeared in blank-DMN or control groups.
- In periodontitis rats, Mino-DMN reduced gingival index, decreased pro-inflammatory factors (IFN-γ, IL-1β, TNF-α), increased anti-inflammatory factors (TGF-β1, IL-10), improved bone parameters, increased osteogenic gene expression (COL1A1, OCN, RUNX2, BMP-2), and lowered osteoclastogenic gene expression compared with untreated, blank-DMN, and topical minocycline groups; compared with Periocline®, most indicators did not differ significantly, except ABL was significantly higher in the Mino-DMN group.
Methods
- Fabrication used a PDMS mold with a 10 × 10 array (300 μm backing side length, 800 μm spacing, 1000 μm height) and a two-step casting micro-molding process: a minocycline/gelatin solution was vacuum dried at 37°C to form tips, then a sucrose-blended HA solution was cast as the backing and freeze-dried.
- Characterization included stereo and fluorescence microscopy, SEM, tensile mechanical testing, ex vivo penetration into rat oral mucosa, in vitro drug release in PBS at 37°C, in vivo fluorescence imaging in SD rats, and Kirby-Bauer antibacterial testing against *P. gingivalis* ATCC33277.
- Animal study: 42 male SD rats (3 weeks old, 80–100 g) were randomized into 7 groups—Control, PD, UT, Mino-DMN (50 μg minocycline, every other day for 4 doses), Blank-DMN, Perio® (2.5 mg Periocline® ointment, every other day for 4 doses), and Mino-Topical (200 μg minocycline topical application, every other day for 4 doses); periodontitis was induced by ligature plus *P. gingivalis* inoculation, and outcomes were assessed by micro-CT, HE staining, qRT-PCR, and ELISA with two-tailed Student’s t-test or one-way ANOVA.
Limitations
- Stated by the paper: potential biases in animal experiments may explain the ABL disparity with Periocline®, and the relatively mild periodontal lesions in rats may have made tooth mobility differences less obvious.
- Evident from the text: the study is limited to a rat model with no human clinical data; sample sizes are small for several assays (e.g., n = 3 for micro-CT, ELISA, and qRT-PCR; n = 6 for clinical measures); treatment follow-up was 4 weeks; and minocycline was used as a model drug, with no long-term safety, scalability, or patient self-administration outcomes reported.
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0 Valid · 1 Not valid · 21 Not checked · 85 Own results and interpretations
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“according to the SEM images (Figure 1e–g), the DMN patch still maintained a good pyramid shape, with sharp tips”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > Fabrication and characterization of the Mino‐DMN patch
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“stimulates bone formation”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > Abstract
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In vivo experiments show Mino‐DMN inhibits pro‐inflammatory factors”
- Also stated in: § INTRODUCTION · plain
“Mino‐DMN effectively enhances alveolar bone height and volume, suppresses the expression of bone‐resorbing factors, and alleviates inflammatory responses in periodontal tissues.”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > Abstract
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § INTRODUCTION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In practical formulation, the actual drug loading achieved was 51 ± 6 μg per patch.”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > Drug loading and release study of the DMN patch
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The results revealed that each tip can exert a force of approximately 0.13 N before fracturing (Figure S5).”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > Mechanical property of the Mino‐DMN patch
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Applying this technology to deliver MNC topically reduces the systemic exposure and bacterial resistance without affecting the normal flora in the gastrointestinal tract. Also, avoids the problematic adverse effects of this drug and enhances the bioavailability due to eliminating the first pass metabolism [27,28,29,30].”
From Formulation and Characterization of PLGA Minocycline Microneedles for Enhanced Skin Deposition and Antibacterial Activity in Acne Treatment (2025) · cites this paper as [28]
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Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > Drug loading and release study of the DMN patch
“In vitro drug release study of the DMN patch involved immersing the patch in PBS at 37°C, while continuously tracking the fluorescence emitted by Rhodamine 6G, a model drug in the DMN patch.”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > MATERIALS AND METHODS > Drug release in vitro and dissolution behavior of the DMN patch
“The drug release study was performed using fluorescein‐loaded DMN patch.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > Mechanical property of the Mino‐DMN patch
“We also observed that Rhodamine 6G was successfully delivered to the inner wall of the created microholes, with the majority of fluorescence concentrated inside the microholes (Figure 1e,f).”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > Fabrication and characterization of the Mino‐DMN patch
“(e–g) Scanning electron micrograph images of minocycline‐loaded DMN patch with porous HA patch backing; In f and g, the DMN patch was vertically cut open to expose its patch backing pores.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > In vivo studies of minocycline MNs for periodontitis treatment
“Additionally, osteoclastogenic genes like NFATc1 and MMP‐2 showed notably lower expression.”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > In vivo studies of minocycline MNs for periodontitis treatment
“The expression levels of (f) MMP‐8, (g) Cathepsin K, (h) NFATc1, (i) BMP‐2, (j) RUNX2, (k) COL1A1, and (l) OCN in the alveolar bone of rats in each group were analyzed using q‐PCR method.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > MATERIALS AND METHODS > Drug release and degradability of the DMN patch in vivo
“In vivo drug release experiments of the DMN patches containing Rhodamine 6G (50 μg) were conducted in SD rats.”
§ Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease > RESULTS AND DISCUSSION > Drug loading and release study of the DMN patch
“(b) Topical application of fluorescein and fluorescein DMN quantified the fluorescence intensity in the gingiva.”
Citations
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Minocycline: Far beyond an Antibiotic
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The cytokine network involved in the host immune response to periodontitis
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Strengthening the Prevention of Periodontal Disease: The WHO Approach
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Regenerative Medicine for Periodontal and Peri-implant Diseases
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Cited by
Liu, J., Zheng, W., Sun, H., González, F. E., Zhou, D., & Xu, X. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114402 · Cited by 19
Bioinspired hydrogel for sustained minocycline release: A superior periodontitis solution
Liu, S., Zheng, W., Wang, L., Zhang, Y., Feng, K., Zhang, Y., Yang, H., Xiao, Y., Sun, C., Liu, X., et al. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.101638 · Cited by 16
Self-citationGong, H., Ma, S., Wang, B., Liu, Y., Xiao, H., Wang, Y., Sun, D., Su, Y., Wang, J., & Zhao, J. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102494 · Cited by 7
Zheng, Y., Xie, Y., Dong, X., Shen, S., Zheng, G., Weng, J., & Yan, Q. (2025) · ACS Applied Polymer Materials · doi:10.1021/acsapm.5c01387 · Cited by 6
Li, W., Zhang, D., Huang, H., Zou, R., Zhang, Z., Sun, P., Chen, H., Yang, L., Jiang, S., & Zeng, X. (2026) · ACS Nano · doi:10.1021/acsnano.5c19988 · Cited by 6
Metadata
- Authors
- Li, H., Wen, X., Gong, X., Wu, Y., Zhao, P., Zhang, Y., Sha, Z., Chang, H., & Chen, X.
- Affiliations
- Zhejiang University Medical College Affiliated Stomatological Hospital (CN)
- Hangzhou Institute of Medicine, Chinese Academy of Sciences (CN)
- Corresponding author
- Chang, Hao
- Chen, Xuepeng
- Venue
- Bioengineering & Translational Medicine
- Publisher
- Wiley
- Published
- 2024-10-20
- Volume
- 10
- Issue
- 2
- Pages
- e10730-e10730
- ISSN
- 2380-6761 (ISSN-L)
- PMC
- PMC11883109
- OpenAlex
- W4403615471
- Semantic Scholar
- 62cce9673d03e291b78abf39bab078c9b4928422
- Cited by
- 17
- References
- 49
- Citations by year
- 2026: 10 · 2025: 7
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bioengineering & Translational Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81400511, 82020108011, 82202329)
- Natural Science Foundation of Zhejiang Province (LY18H140001)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- minocycline, periodontitis, local drug delivery, freeze-drying, vacuum drying, bone formation, anti-inflammatory activity, medication adherence
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- The paper
- Li, H., Wen, X., Gong, X., Wu, Y., Zhao, P., Zhang, Y., Sha, Z., Chang, H., & Chen, X. (2025). Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease. Bioengineering & Translational Medicine. https://doi.org/10.1002/btm2.10730
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