Skip to content
2000
Volume 22, Issue 8
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Introduction

Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms.

Methods

In this study, responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS).

Results

and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis-associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells.

Conclusion

This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018305286240502060504
2024-05-03
2026-01-30

  • From This Site

    /content/journals/cdd/10.2174/0115672018305286240502060504
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. PretzlB. SälzerS. EhmkeB. SchlagenhaufU. DannewitzB. DommischH. EickholzP. SchneiderJ.Y. Administration of systemic antibiotics during non-surgical periodontal therapy—A consensus report.Clin. Oral Investig.20192373073308510.1007/s00784‑018‑2727‑030374830
     [Google Scholar]
  2. HiginoT. FrançaR. Drug-delivery nanoparticles for bone-tissue and dental applications.Biomed. Phys. Eng. Express20228404200110.1088/2057‑1976/ac682c35439740
     [Google Scholar]
  3. KaurH. GroverV. MalhotraR. GuptaM. Evaluation of Curcumin Gel as Adjunct to Scaling & Root Planing in Management of Periodontitis- Randomized Clinical & Biochemical Investigation.Infect. Disord. Drug Targets201919217117829852877
     [Google Scholar]
  4. LiY ChoM H LeeS S Hydroxychloroquine-loaded hollow mesoporous silica nanoparticles for enhanced autophagy inhibition and radiation therapy.J Control Release2020325100110
     [Google Scholar]
  5. BeaganA. LahmadiS. AlghamdiA. HalwaniM. AlmeataqM. AlhazaaA. AlotaibiK. AlswielehA. Glucosamine Modified the Surface of pH-Responsive Poly(2-(diethylamino)ethyl Methacrylate) Brushes Grafted on Hollow Mesoporous Silica Nanoparticles as Smart Nanocarrier.Polymers20201211274910.3390/polym1211274933233772
     [Google Scholar]
  6. AlotaibiK.M. AlmethenA.A. BeaganA.M. AlfhaidL.H. AhamedM. El-ToniA.M. AlswielehA.M. Poly(oligo(ethylene glycol) methyl ether methacrylate) Capped pH-Responsive Poly(2-(diethylamino)ethyl methacrylate) Brushes Grafted on Mesoporous Silica Nanoparticles as Nanocarrier.Polymers202113582310.3390/polym1305082333800258
     [Google Scholar]
  7. WangK LiX WangH Evaluation on redox-triggered degradation of thioether-bridged hybrid mesoporous organosilica nanoparticles.Colloid surface a202160812556610.1016/j.colsurfa.2020.125566
     [Google Scholar]
  8. MöllerK. BeinT. Degradable Drug Carriers: Vanishing Mesoporous Silica Nanoparticles.Chem. Mater.201931124364437810.1021/acs.chemmater.9b00221
     [Google Scholar]
  9. BeamerG L SeaverB P Acute Exposure to Crystalline Silica Reduces Macrophage Activation in Response to Bacterial Lipoproteins.Front. Immunol.2016749
     [Google Scholar]
  10. SolimanG.M. Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges.Int. J. Pharm.20175231153210.1016/j.ijpharm.2017.03.01928323096
     [Google Scholar]
  11. MissaouiN.W. ArnoldR.D. CummingsB.S. Safe Nanoparticles: Are We There Yet?Int. J. Mol. Sci.202022138510.3390/ijms2201038533396561
     [Google Scholar]
  12. WangX. ZhongX. LiJ. LiuZ. ChengL. Inorganic nanomaterials with rapid clearance for biomedical applications.Chem. Soc. Rev.202150158669874210.1039/D0CS00461H34156040
     [Google Scholar]
  13. GandhiN S TekadeR K ChouguleM B Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: Current progress and advances.J. Control Release.201419423856
     [Google Scholar]
  14. YangJ. DaiD. LouX. MaL. WangB. YangY.W. Supramolecular nanomaterials based on hollow mesoporous drug carriers and macrocycle-capped CuS nanogates for synergistic chemo-photothermal therapy.Theranostics202010261562910.7150/thno.4006631903141
     [Google Scholar]
  15. YanT HeJ LiuR Chitosan capped pH-responsive hollow mesoporous silica nanoparticles for targeted chemo-photo combination therapy.Carbohyd. Polym.202023111570610.1016/j.carbpol.2019.115706
     [Google Scholar]
  16. BindiniE. RamirezM.L.A. In Vivo Tracking of the Degradation of Mesoporous Silica through 89 Zr Radio-Labeled Core-Shell Nanoparticles.Small20211730e2101519
     [Google Scholar]
  17. ZhaoW FuY ChenY Effective fenton catalyst from controllable framework doping of Fe in porous silica spheres.Micropor. Mesopor. Mat.202131211070410.1016/j.micromeso.2020.110704
     [Google Scholar]
  18. HaoY. ZhengC. SongQ. ChenH. NanW. WangL. ZhangZ. ZhangY. Pressure-driven accumulation of Mn-doped mesoporous silica nanoparticles containing 5-aza-2-deoxycytidine and docetaxel at tumours with a dry cupping device.J. Drug Target.202129890090910.1080/1061186X.2021.189211733655819
     [Google Scholar]
  19. LiX ZhangX ZhaoY Fabrication of biodegradable Mn-doped mesoporous silica nanoparticles for pH/redox dual response drug delivery.J. Inorg. Biochem.2020202110887
     [Google Scholar]
  20. WangX LiX ItoA Biodegradable Metal Ion-Doped Mesoporous Silica Nanospheres Stimulate Anticancer Th1 Immune Response in Vivo.Acs Appl Mater Inter2017950435384410.1021/acsami.7b16118
     [Google Scholar]
  21. HeY ZengB LiangS Synthesis of pH-Responsive Biodegradable Mesoporous Silica-Calcium Phosphate Hybrid Nanoparticles as a High Potential Drug Carrier.Acs. Appl. Mater. Inter.201795144402910.1021/acsami.7b16787
     [Google Scholar]
  22. KimuraA. KunimatsuR. YoshimiY. TsukaY. AwadaT. HorieK. GunjiH. AbeT. NakajimaK. KitagawaM. MiyauchiM. TakataT. TanimotoK. Baicalin Promotes Osteogenic Differentiation of Human Cementoblast Lineage Cells Via the Wnt/β Catenin Signaling Pathway.Curr. Pharm. Des.201924333980398710.2174/138161282466618111610351430693853
     [Google Scholar]
  23. SathiyavimalS VasantharajS LewisoscarF Natural organic and inorganic–hydroxyapatite biopolymer composite for biomedical applications.Prog. Org. Coat.202014710585810.1016/j.porgcoat.2020.105858
     [Google Scholar]
  24. PandaS. BiswasC.K. PaulS. A comprehensive review on the preparation and application of calcium hydroxyapatite: A special focus on atomic doping methods for bone tissue engineering.Ceram. Int.20214720281222814410.1016/j.ceramint.2021.07.100
     [Google Scholar]
  25. WangG LuT ZhangX Structure and properties of cellulose/HAP nanocomposite hydrogels.Int. J. Biol. Macromol.202118637784
     [Google Scholar]
  26. ChenM HuJ BianC pH-Responsive and Biodegradable ZnO-Capped Mesoporous Silica Composite Nanoparticles for Drug Delivery.Materials202013183950
     [Google Scholar]
  27. HaoX. HuX. ZhangC. ChenS. LiZ. YangX. LiuH. JiaG. LiuD. GeK. LiangX.J. ZhangJ. Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved Degradability by Hydroxyapatite.ACS Nano20159109614962510.1021/nn507485j26316321
     [Google Scholar]
  28. XuS. HuB. DongT. ChenB.Y. XiongX.J. DuL.J. LiY.L. ChenY.L. TianG.C. BaiX.B. LiuT. ZhouL.J. ZhangW.C. LiuY. DingQ.F. ZhangX.Q. DuanS.Z. Alleviate Periodontitis and Its Comorbidity Hypertension using a Nanoparticle-Embedded Functional Hydrogel System.Adv. Healthc. Mater.20231220220333710.1002/adhm.20220333736972711
     [Google Scholar]
  29. YinI X The Antibacterial Mechanism of Silver Nanoparticles and Its Application in Dentistry.Int. J. Nanomedicine.202015255562
     [Google Scholar]
  30. TangS. ZhengJ. Antibacterial Activity of Silver Nanoparticles: Structural Effects.Adv. Healthc. Mater.2018713170150310.1002/adhm.20170150329808627
     [Google Scholar]
  31. LinJ HeZ LiuF Hybrid Hydrogels for Synergistic Periodontal Antibacterial Treatment with Sustained Drug Release and NIR-Responsive Photothermal Effect.Int. J. Nanomedicine.202015537787
     [Google Scholar]
  32. WuS.H. MouC.Y. LinH.P. Synthesis of mesoporous silica nanoparticles.Chem. Soc. Rev.20134293862387510.1039/c3cs35405a23403864
     [Google Scholar]
  33. MouJ. LiuZ. LiuJ. LuJ. ZhuW. PeiD. Hydrogel containing minocycline and zinc oxide-loaded serum albumin nanopartical for periodontitis application: Preparation, characterization and evaluation.Drug Deliv.201926117918710.1080/10717544.2019.157112130822158
     [Google Scholar]
  34. ChoY.D. KimK.H. RyooH.M. LeeY.M. KuY. SeolY.J. Recent Advances of Useful Cell Sources in the Periodontal Regeneration.Curr. Stem Cell Res. Ther.20191413810.2174/1574888X1366618081611345630112999
     [Google Scholar]
  35. TeughelsW FeresM OudV Adjunctive effect of systemic antimicrobials in periodontitis therapy: A systematic review and meta-analysis.J. Clin. Periodontol.202047S2225781
     [Google Scholar]
  36. HsuY.T. NairM. AngelovN. LallaE. LeeC.T. Impact of diabetes on clinical periodontal outcomes following non‐surgical periodontal therapy.J. Clin. Periodontol.201946220621710.1111/jcpe.1304430536853
     [Google Scholar]
  37. HellebergH.S. FliervoetL.A.L. FanøM. SchmittM. AntopolskiM. UrttiA. NielsenH.M. Exploring the mucoadhesive behavior of sucrose acetate isobutyrate: A novel excipient for oral delivery of biopharmaceuticals.Drug Deliv.201926153254110.1080/10717544.2019.160686631090468
     [Google Scholar]
  38. ChatzopoulosG.S. KoidouV.P. TsalikisL. Local drug delivery in the treatment of furcation defects in periodontitis: A systematic review.Clin. Oral Investig.202327395597010.1007/s00784‑023‑04871‑036729235
     [Google Scholar]
  39. SanzM. CerielloA. BuysschaertM. ChappleI. DemmerR.T. GrazianiF. HerreraD. JepsenS. LioneL. MadianosP. MathurM. MontanyaE. ShapiraL. TonettiM. VeghD. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology.J. Clin. Periodontol.201845213814910.1111/jcpe.1280829280174
     [Google Scholar]
  40. TelesF. CollmanR.G. MominkhanD. WangY. Viruses, periodontitis, and comorbidities.Periodontol. 2000202289119020610.1111/prd.1243535244970
     [Google Scholar]
  41. SanzM. CastilloM.A. JepsenS. JuanateyG.J.R. D’AiutoF. BouchardP. ChappleI. DietrichT. GotsmanI. GrazianiF. HerreraD. LoosB. MadianosP. MichelJ.B. PerelP. PieskeB. ShapiraL. ShechterM. TonettiM. VlachopoulosC. WimmerG. Periodontitis and cardiovascular diseases: Consensus report.J. Clin. Periodontol.202047326828810.1111/jcpe.1318932011025
     [Google Scholar]
  42. SanzM. KornmanK. Periodontitis and adverse pregnancy outcomes: Consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases.J. Periodontol.2013844S164S16923631576
     [Google Scholar]
  43. YangC. ZhangM. MerlinD. Advances in plant-derived edible nanoparticle-based lipid nano-drug delivery systems as therapeutic nanomedicines.J. Mater. Chem. B Mater. Biol. Med.2018691312132110.1039/C7TB03207B30034807
     [Google Scholar]
  44. ZhangZ YuY ZhuG The Emerging Role of Plant-Derived Exosomes-Like Nanoparticles in Immune Regulation and Periodontitis Treatment.Front. Immunol.20221389674510.3389/fimmu.2022.896745
     [Google Scholar]
  45. HuangH. PanW. WangY. KimH.S. ShaoD. HuangB. HoT.C. LaoY.H. QuekC.H. ShiJ. ChenQ. ShiB. ZhangS. ZhaoL. LeongK.W. Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis.Nat. Commun.2022131592510.1038/s41467‑022‑33492‑636207325
     [Google Scholar]
  46. QiaoX TangJ DouL Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats.Int. J. Nanomedicine.202318468370310.2147/IJN.S420967
     [Google Scholar]
  47. BuzeaC. PachecoI.I. RobbieK. Nanomaterials and nanoparticles: Sources and toxicity.Biointerphases200724MR17MR7110.1116/1.281569020419892
     [Google Scholar]
  48. PanW. ZhangH.J. ZhangY.F. WangM. TsuiM.T.K. YangL. MiaoA.J. Silica nanoparticle accumulation in plants: Current state and future perspectives.Nanoscale20231537150791509110.1039/D3NR02221H37697950
     [Google Scholar]
  49. HuangX. TengX. ChenD. TangF. HeJ. The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function.Biomaterials201031343844810.1016/j.biomaterials.2009.09.06019800115
     [Google Scholar]
  50. HuangX. LiL. LiuT. HaoN. LiuH. ChenD. TangF. The shape effect of mesoporous silica nanoparticles on biodistribution, clearance, and biocompatibility in vivo.ACS Nano2011575390539910.1021/nn200365a21634407
     [Google Scholar]
  51. LiL. LiuT. FuC. TanL. MengX. LiuH. Biodistribution, excretion, and toxicity of mesoporous silica nanoparticles after oral administration depend on their shape.Nanomedicine20151181915192410.1016/j.nano.2015.07.00426238077
     [Google Scholar]
  52. ShangL NienhausK NienhausG U Engineered nanoparticles interacting with cells: Size matters.J. Nanobiotechnol.2014125
     [Google Scholar]
  53. LiJ. ShenS. KongF. JiangT. TangC. YinC. Effects of pore size on in vitro and in vivo anticancer efficacies of mesoporous silica nanoparticles.RSC Advances2018843246332464010.1039/C8RA03914C35539161
     [Google Scholar]
  54. CroissantJ G BrinkerC J Biodegradable Silica-Based Nanoparticles: Dissolution Kinetics and Selective Bond Cleavage.Enzymes201843181214
     [Google Scholar]
  55. LINDéNM. Biodistribution and Excretion of Intravenously Injected Mesoporous Silica Nanoparticles: Implications for Drug Delivery Efficiency and Safety.Enzymes20184315580
     [Google Scholar]
  56. LiZ. BarnesJ.C. BosoyA. StoddartJ.F. ZinkJ.I. Mesoporous silica nanoparticles in biomedical applications.Chem. Soc. Rev.20124172590260510.1039/c1cs15246g22216418
     [Google Scholar]
  57. NapierskaD. ThomassenL.C.J. RabolliV. LisonD. GonzalezL. VoldersK.M. MartensJ.A. HoetP.H. Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells.Small20095784685310.1002/smll.20080046119288475
     [Google Scholar]
  58. NishimoriH. KondohM. IsodaK. TsunodaS. TsutsumiY. YagiK. Silica nanoparticles as hepatotoxicants.Eur. J. Pharm. Biopharm.200972349650110.1016/j.ejpb.2009.02.00519232391
     [Google Scholar]
  59. McCarthyJ. StępniakI.I. CorbalanJ.J. RadomskiM.W. Mechanisms of toxicity of amorphous silica nanoparticles on human lung submucosal cells in vitro: protective effects of fisetin.Chem. Res. Toxicol.201225102227223510.1021/tx300288422931364
     [Google Scholar]
  60. IannazzoD. PistoneA. SalamòM. GalvagnoS. RomeoR. GiofréS.V. BrancaC. VisalliG. Di PietroA. Graphene quantum dots for cancer targeted drug delivery.Int. J. Pharm.20175181-218519210.1016/j.ijpharm.2016.12.06028057464
     [Google Scholar]
  61. ThenmozhiR. MoorthyM.S. SivaguruJ. ManivasaganP. BharathirajaS. OhY.O. OhJ. Synthesis of Silica-Coated Magnetic Hydroxyapatite Composites for Drug Delivery Applications.J. Nanosci. Nanotechnol.20191941951195810.1166/jnn.2019.1539930486935
     [Google Scholar]
  62. ChenX. ZhangQ. LiJ. YangM. ZhaoN. XuF.J. Rattle-Structured Rough Nanocapsules with in-Situ -Formed Gold Nanorod Cores for Complementary Gene/Chemo/Photothermal Therapy.ACS Nano20181265646565610.1021/acsnano.8b0144029870655
     [Google Scholar]
  63. JungW.J. ParkR.D. Bioproduction of chitooligosaccharides: Present and perspectives.Mar. Drugs201412115328535610.3390/md1211532825353253
     [Google Scholar]
  64. CroissantJ.G. FatieievY. KhashabN.M. Degradability and Clearance of Silicon, Organosilica, Silsesquioxane, Silica Mixed Oxide, and Mesoporous Silica Nanoparticles.Adv. Mater.2017299160463410.1002/adma.20160463428084658
     [Google Scholar]
  65. ZhangT. QiuY. SongJ. ZhouP. LiaoH. ChengY. WuX. Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment.Drug Deliv.202128162063310.1080/10717544.2021.190202033779441
     [Google Scholar]
  66. DaiT. TanakaM. HuangY.Y. HamblinM.R. Chitosan preparations for wounds and burns: Antimicrobial and wound-healing effects.Expert Rev. Anti Infect. Ther.20119785787910.1586/eri.11.5921810057
     [Google Scholar]
  67. ZhengS ZhouC YangH Melatonin Accelerates Osteoporotic Bone Defect Repair by Promoting Osteogenesis-Angiogenesis Coupling.Front. Endocrinol.20221382666010.3389/fendo.2022.826660
     [Google Scholar]
  68. PanL ZhangC ZhangH Osteoclast-Derived Exosomal miR-5134-5p Interferes with Alveolar Bone Homeostasis by Targeting the JAK2/STAT3 Axis.Int. J. Nanomedicine.202318372744
     [Google Scholar]
  69. ChenY. WangH. NiQ. WangT. BaoC. GengY. LuY. CaoY. LiY. LiL. XuY. SunW. B-Cell–Derived TGF-β1 Inhibits Osteogenesis and Contributes to Bone Loss in Periodontitis.J. Dent. Res.2023102776777610.1177/0022034523116100537082865
     [Google Scholar]
  70. MaZ. GuoK. ChenL. ChenX. ZouD. YangC. Role of periosteum in alveolar bone regeneration comparing with collagen membrane in a buccal dehiscence model of dogs.Sci. Rep.2023131250510.1038/s41598‑023‑28779‑736781898
     [Google Scholar]
  71. ZhaoJ WeiY XiongJ A multiple controlled-release hydrophilicity minocycline hydrochloride delivery system for the efficient treatment of periodontitis.Int. J. Pharm.202363612280210.1016/j.ijpharm.2023.122802
     [Google Scholar]
  72. VB.U. SaygunI. BalV. OzcanE. OzkanK.C. TorunD. AvcuF. KantarcıA. Effect of antioxidant lycopene on human osteoblasts.Clin. Oral Investig.20222741637164310.1007/s00784‑022‑04789‑z36416948
     [Google Scholar]
  73. MaiaC.M D BarbozaC A BJunior SouzaS.C A Microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite: Therapeutic potential and effects on bone regeneration.Int. J. Nanomedicine.20191445597110.2147/IJN.S201631
     [Google Scholar]
  74. XuX C Simvastatin prevents alveolar bone loss in an experimental rat model of periodontitis after ovariectomy.J Transl Med201412284
     [Google Scholar]
  75. HaradaS. TakahashiN. Control of bone resorption by RANKL-RANK system.Clin. Calcium20112181121113021814016
     [Google Scholar]
  76. WangH. AshtonR. HenselJ.A. LeeJ.H. KhattarV. WangY. DeshaneJ.S. PonnazhaganS. RANKL-Targeted Combination Therapy with Osteoprotegerin Variant Devoid of TRAIL Binding Exerts Biphasic Effects on Skeletal Remodeling and Antitumor Immunity.Mol. Cancer Ther.202019122585259710.1158/1535‑7163.MCT‑20‑037833199500
     [Google Scholar]
/content/journals/cdd/10.2174/0115672018305286240502060504
Loading
A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy
Curr. Drug Deliv. 22, 1143 (2025); https://doi.org/10.2174/0115672018305286240502060504
/content/journals/cdd/10.2174/0115672018305286240502060504
/content/journals/cdd/10.2174/0115672018305286240502060504
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): antibacterial; biodegradation; bone formation; in vitro cytotoxicity; Mesoporous silica nanoparticle; periodontitis therapy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test