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Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment
Open accessAbstract
Minocycline hydrochloride (MINO) has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and osteogenesis effects; however, high levels of MINO administered during the treatment halt the formation of new bone. Therefore, the purpose of the present study was to prepare a MINO-microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot to reduce the burst release of MINO and ensure antibacterial and osteogenesis effects of MINO in the treatment of periodontitis. Uniform microspheres, approximately 5 µm size, with a slightly rough surface and different MINO loading (10, 12, and 14%) were prepared, and the microspheres were added into SAIB, after which the burst release significantly decreased from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45%, respectively, and the release from all the MINO-microspheres/SAIB hybrid depots lasted for 77 days. In addition, cytotoxicity test showed that the MINO-microsphere with 12% drug loading promoted the proliferation of osteoblasts the most and was subsequently used in vivo experiments. Moreover, in the model of ligatured-induced periodontitis in SD rats, the MINO-microsphere/SAIB hybrid depot not only significantly increased the alveolar bone height and bone volume but also reduced the inflammation of the periodontal tissue. Additionally, it also inhibited the expression of the receptor activator of nuclear factor-kappa B ligand (RANKL) and promoted the expression of osteoprotegerin (OPG).. These results indicated that the MINO-microsphere/SAIB hybrid depot might be promising in the treatment of periodontitis.
Overview
CoChat Summary
TL;DR
A minocycline hydrochloride (MINO)-loaded PLGA/PEG microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot was developed to reduce MINO burst release while retaining antibacterial and osteogenic effects for periodontitis. In ligature-induced periodontitis in SD rats, the depot improved alveolar bone outcomes and reduced periodontal inflammation compared with ligation controls.
Key findings
- Adding MINO-microspheres to SAIB markedly reduced first-day burst release: from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45% (abstract; the results section reports the third pair as 73.75 to 4.45%), with release lasting 77 days.
- The 12% MINO-microsphere group promoted osteoblast proliferation the most in CCK-8 assays and was selected for in vivo testing.
- In SD rats with ligature-induced periodontitis, the MINO-microsphere/SAIB depot significantly increased alveolar bone height and bone volume/tissue volume (BV/TV) and reduced periodontal tissue inflammation versus ligation and ligation + M-SAIB groups.
- The depot inhibited RANKL expression and promoted OPG expression at 3 and 6 weeks.
Methods
- MINO-loaded PLGA/PEG microspheres (0%, 10%, 12%, and 14% w/w MINO relative to PLGA) were prepared by electrospraying, characterized by SEM, UV-Vis, contact angle, confocal microscopy, DSC, and FTIR, then dispersed into SAIB/ethanol to form hybrid depots.
- In vitro release, degradation, and porosity were measured over time; osteoblast cytotoxicity/proliferation was assessed by CCK-8 using rat calvarial osteoblasts.
- In vivo, 7-week-old female SD rats were assigned to five groups (n = 5): control, ligation, ligation + M-SAIB, ligation + MINO-M-SAIB, and ligation + Periocline®; outcomes included periodontal parameters, micro-CT, H&E histology, and immunohistochemistry for OPG/RANKL, analyzed by one-way ANOVA with Student–Newman–Keuls test.
Limitations
- The paper does not state a limitations section.
- Evident from the text: the study is preclinical only, using in vitro assays and a rat ligature-induced periodontitis model, with n = 5 per group and endpoints at 3 and 6 weeks; no human clinical, long-term safety, or systemic exposure data are reported.
- The abstract and results section report slightly different burst-release values for the third microsphere group (73.35% vs 73.75%), which the text does not reconcile.
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Claims the paper makes
0 Valid · 0 Not valid · 39 Not checked · 93 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
“cytotoxicity test showed that the MINO-microsphere with 12% drug loading promoted the proliferation of osteoblasts the most”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > 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
“significantly increased the alveolar bone height and bone volume”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > 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.
- Rests on an assumption not shown here.
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
“These results illustrate that the hydrophilicity of the micospheres increased with increasing concentration of MINO (p < .05).”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > Characteristics of MINO-microspheres and MINO-M-SAIB hybrid depots
plainstates a cause- 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
“Among the microspheres with different MINO loading capacities, the differences in the diameter were not statistically significant (p > .05).”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > Characteristics of MINO-microspheres and MINO-M-SAIB hybrid depots
plainn = 100- 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 burst release significantly decreased from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45%, respectively”
- Also stated in: § In vitro release of MINO-microspheres and MINO-M-SAIB hybrid depots · plain
“the initial burst release decreased significantly from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.75 to 4.45% on the first day, respectively.”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > 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: § In vitro release of MINO-microspheres and MINO-M-SAIB hybrid depots · plain
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- Probably not a substantial claim. 11
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
“Both in‐development minocycline formulations and clinically utilized medications currently necessitate specialized delivery devices for administration into periodontal pockets.”
From Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease (2025) · cites this paper as [28]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Methods and materials > Animal experiments
“a 0.2-mm-diameter orthodontic steel wire was ligated around the first molar of the rat mandible for 4 weeks.”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Methods and materials > Animal experiments
“The specimens (the alveolar bone including the first, second, and third molars of rat maxillary) were collected and fixed in 4% paraformaldehyde for micro-CT scanning”
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
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > In vitro release of MINO-microspheres and MINO-M-SAIB hybrid depots
“The Ritger-Peppas equation showed high R2 value (R2 > .99) to all kinetic data”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > In vitro release of MINO-microspheres and MINO-M-SAIB hybrid depots
“| Ritger-Peppas model | R2=.993 | R2=.993 | R2=.992 | R2=.989 |”
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
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > Characteristics of MINO-microspheres and MINO-M-SAIB hybrid depots
“| M2 | 5.297 ± 0.515 | 9.72% | 90 ± 0.25 | 11.148 ± 0.049 | 57.24 ± 1.45 |”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > Characteristics of MINO-microspheres and MINO-M-SAIB hybrid depots
“the drug loading of M1, M2, and M3 were 8.71 ± 0.012%, 11.148 ± 0.077%, and 12.64 ± 0.03%”
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
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Abstract
“from 73.35 to 4.45%, respectively”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > In vitro release of MINO-microspheres and MINO-M-SAIB hybrid depots
“from 73.75 to 4.45% on the first day, respectively.”
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
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > In vitro release of MINO-microspheres and MINO-M-SAIB hybrid depots
“After 10 days, the release profiles of the depots were all featured by a sustained rate (of >0.38% per day) until the 77th day.”
§ Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment > Results > In vitro release of MINO-microspheres and MINO-M-SAIB hybrid depots
“| Slopea | 1.42998 ± 0.00588 | 0.37367 ± 0.00135 | 1.49536 ± 0.00615 | 0.37978 ± 0.00138 | 1.62893 ± 0.0067 | 0.35531 ± 0.00133 | 1.7763 ± 0.01286 | 0.34716 ± 0.0022 |”
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Citations
Cites
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Biodegradation and biocompatibility of PLA and PLGA microspheres
Anderson, J. M., & Shive, M. S. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.004 · Cited by 814
Peppas, N. A., Duncan, R., Wnek, G. E., Hoffman, A. S., Gao, G. H., Kim, S. W., Lee, D. S., Hadjiargyrou, M., Touitou, E., Ainbinder, D., et al. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.07.012 · Cited by 787
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How Autocatalysis Accelerates Drug Release from PLGA-Based Microparticles: A Quantitative Treatment
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Research works printed but not linked: 1
- 10.1080/10717544.2019.1568620 · DOI · Paper page
Cited by
Song, C., Huang, D., Zhao, C., & Zhao, Y. (2022) · Advanced Science · doi:10.1002/advs.202202829 · Cited by 57
Yi, Y., Song, J., Zhou, P., Shu, Y., Liang, P., Liang, H., Liu, Y., Yuan, X., Shan, X., & Wu, X. (2024) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2024.122039 · Cited by 51
Self-citationWu, H., Li, Y., Shi, L., Liu, Y., & Shen, J. Q. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202403206 · Cited by 44
Li, Y., He, X., Luo, G., Zhao, J., Bai, G., & Xu, D. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1556688 · Cited by 39
Song, Y. W., Nam, J., Kim, J., Lee, Y., Choi, J., Min, H. S., Yang, H., Cho, Y., Hwang, S., Son, J., et al. (2025) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2024.122976 · Cited by 33
Metadata
- Authors
- Zhang, T., Qiu, Y., Song, J., Zhou, P., Liao, H., Cheng, Y., & Wu, X.
- Affiliations
- Stomatological Hospital of Chongqing Medical University (CN)
- Stomatological Hospital of Chongqing Medical University, Chongqing, China
- Corresponding author
- Wu, Xiaohong
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2021-01
- Volume
- 28
- Issue
- 1
- Pages
- 620-633
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC8008938
- OpenAlex
- W3147019705
- Cited by
- 36
- References
- 52
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 6 · 2023: 8 · 2022: 3
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (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 (81970914)
- Institutions of Higher Education in Chongqing
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Keywords
- minocycline hydrochloride, periodontitis, electrospraying, microspheres, sucrose acetate isobutyrate, sustained drug release, burst release, bone formation, osteoblast proliferation, alveolar bone regeneration, RANKL, osteoprotegerin, ligature-induced periodontitis, periodontal inflammation
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Anti-Bacterial Agents, Chemistry, Pharmaceutical, Delayed-Action Preparations, Drug Implants, Microspheres, Minocycline, Osteoblasts, Osteogenesis, Periodontitis, Sucrose, Rats, Sprague-Dawley, Rats, Osteoprotegerin, Receptor Activator of Nuclear Factor-kappa B, Drug Liberation
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- CoChat. (2026). Citation check: Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment. https://app.cochat.ai/papers/10.1080/10717544.2021.1902020
- The paper
- Zhang, T., Qiu, Y., Song, J., Zhou, P., Liao, H., Cheng, Y., & Wu, X. (2021). Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment. Drug Delivery. https://doi.org/10.1080/10717544.2021.1902020
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