Adjunctive Drug-Loaded Gel in the Treatment of Periodontitis: A Systematic Evaluation and Meta-Analysis
-
Zhige Li
,
Xin Yang
,
Jiao Wang
,
Ziyang Qin
,
Yucheng Meng
,
Baoping Zhang
Abstract
Background: This meta-analysis aimed to systematically investigate the efficacy of drug-loaded gel adjuncts in the treatment of periodontitis.
Methods: A comprehensive search was conducted in six databases, i.e., the China National Knowledge Infrastructure, WanFang Data, VIP Chinese Science and Technology Periodical Database, China Biology Medicine Disc, Cochrane Library, PubMed, and Web of Science, from the inception until Jun 2023. The search focused on randomized controlled trials that examined the application of drug-loaded gels in the treatment of periodontitis. Periodontal probing depth and clinical attachment level were the primary and secondary outcomes, respectively. Stata 15.0 and Review Manager 5.4 were employed to perform the meta-analysis using the selected articles that met the predefined criteria.
Results: This study included 16 randomized controlled trials involving 1146 participants. Subgroup analyses based on the follow-up period revealed that the gel-based drug-assisted subgingival root planning intervention had more favorable effects on periodontal probing depth (standardized mean difference=0.50, 95% confidence interval=[0.32, 0.68], I2=56.0%, P=0.001) and clinical attachment level (standardized mean difference=0.47, 95% confidence interval=[0.29, 0.66], I2=57.0%, P=0.0007) than the subgingival root planning intervention alone. However, subgroup analysis based on the action mechanism of gel drugs showed no statistically significant differences in periodontal probing depth and clinical attachment level between groups.
Conclusion: The application of the drug-loaded gel as adjunctive therapy for periodontitis effectively reduced periodontal probing depth and promoted clinical attachment level recovery. The findings provide evidence-based support for the efficacy, security, and rational use of drug-loaded gel in the treatment of periodontitis.
1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392(10159): 1789–1858.
2. Chen M, Cai W (2019). Oxidative stress-related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: A systematic review and meta-analysis. J Clin Periodontol, 46(6): 608–622.
3. Kavarthapu A, Gurumoorthy K (2021). Linking chronic periodontitis and oral cancer: A review. Oral Oncol, 121: 105375.
4. Wang RP, Ho YS (2019). Systemic inflammation linking chronic periodontitis to cognitive decline. Brain Behav Immun, 81: 63–73.
5. Sayed EN, Baeumer A (2019). Twenty years later: Oral health-related quality of life and standard of treatment in patients with chronic periodontitis. J Periodontol, 90(4): 323–330.
6. Ilango P, Mahendra J (2021). Evidence linking the role of periodontal viruses in coronary artery disease with and without periodontitis. J Periodontol, 92(1): 113–122.
7. Takeguchi A, Miyazawa, K (2021). Effects of a β2-adrenergic receptor blocker on experimental periodontitis in spontaneously hypertensive rats. Life Sci, 277: 119593.
8. Choi S, Kim K (2019). Association of Chronic Periodontitis on Alzheimer's Disease or Vascular Dementia. J Am Geriatr Soc, 67(6): 1234–1239.
9. Fleury V, Zekeridou A (2021). Oral Dysbiosis and Inflammation in Parkinson's Disease . J Parkinsons Dis, 11(2): 619-31.
10. Zhao X, Yang Y (2022). Injectable hydrogels with high drug loading through B-N coordination and ROS-triggered drug release for efficient treatment of chronic periodontitis in diabetic rats. Biomaterials, 282: 121387.
11. AlSakr A, Blanchard S (2021). Association between intracranial carotid artery calcifications and periodontitis: A cone-beam computed tomography study. J Periodontol, 92(10): 1402–1409.
12. Liu M, Liu Q (2021). LncRNA LTSCCAT promotes tongue squamous cell carcinoma metastasis via targeting the miR-103a-2-5p/SMYD3/TWIST1 axis. Cell Death Dis, 12(2): 144.
13. Yao Y, Shen X (2021). Periodontal Pathogens Promote Oral Squamous Cell Carcinoma by Regulating ATR and NLRP3 Inflammasome. Front Oncol, 11: 722797.
14. D'Aiuto F, Gkranias N (2018). Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial. Lancet Diabetes Endocrinol, 6(12): 954–965.
15. Kaku M, Matsuda S (2021). Generalized periodontitis treated with periodontal, orthodontic, and prosthodontic therapy: A case report. World J Clin Cases, 9(21): 6110–6124.
16. Fang F, Gao B (2021). Efficacy of root canal therapy combined with basic periodontal therapy and its impact on inflammatory responses in patients with combined periodontal-endodontic lesions. Am J Transl Res, 13(12): 14149–14156.
17. Cecoro G, Piccirillo A (2021). Efficacy of locally delivered statins as an adjunct to scaling and root planning in the treatment of periodontitis: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci, 25(18): 5737–5754.
18. Pretzl B, Sälzer S (2019). Administration of systemic antibiotics during non-surgical periodontal therapy-a consensus report. Clin Oral Investig, 23(7): 3073–3085.
19. Almoshari Y, Ren R (2020). GSK3 inhibitor-loaded osteotropic Pluronic hydrogel effectively mitigates periodontal tissue damage associated with experimental periodontitis. Biomaterials, 261: 120293.
20. Naga K, Ideguchi H (2020). An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during resolution of experimental periodontitis. FASEB J, 34(10): 13726–13740.
21. Gupta R, Pandit N (2008). Comparative evaluation of subgingivally delivered 10% doxycycline hyclate and xanthan-based chlorhexidine gels in the treatment of chronic periodontitis. J Contemp Dent Pract, 9(7): 25–32.
22. Ilyes I, Rusu D (2023). A Placebo-Controlled Trial to Evaluate Two Locally Delivered Antibiotic Gels (Piperacillin Plus Tazobactam vs. Doxycycline) in Stage III-IV Periodontitis Patients. Medicina (Kaunas), 59(2): 303.
23. Flemmig TF, Petersilka G (2011). Efficacy and safety of adjunctive local moxifloxacin delivery in the treatment of periodontitis. J Periodontol, 82(1): 96–105.
24. Radulescu V, Boariu MI (2022). Clinical and microbiological effects of a single application of sodium hypochlorite gel during subgingival re-instrumentation: a triple-blind randomized placebo-controlled clinical trial. Clin Oral Investig, 26(11): 6639–6652.
25. Liang FZ, Wang JL (2020). Effect of ultrasonic subgingival scaling combined with hyaluronic acid gel treatment on the efficacy of periodontitis and the expression of CRP and VEGF in the elderly. Chinese Journal of Gerontology, 40(19): 4146-4149.
26. Dong ZH, Shi SG (2012). Application of slow-release chlorhexidine gel in the treatment of chronic periodontitis. Journal of Endodontics and Periodontology. 22(10): 594-6.
27. Kadadasu R, Atchuta A (2020). Clinicomicrobiological evaluation of the efficacy of local delivery of moxifloxacin and ibuprofen gel as an adjunct to scaling and root planing in chronic periodontitis patients. J Oral Maxillofac Pathol, 24(1): 26–32.
28. Mahendra J, Mahendra L (2013). Clinical effects of subgingivally delivered spirulina gel in chronic periodontitis cases: a placebo controlled clinical trial. J Clin Diagn Res, 7(10): 2330–2333.
29. Matesanz P, Herrera D (2013). A randomized clinical trial on the clinical and microbiological efficacy of a xanthan gel with chlorhexidine for subgingival use. Clin Oral Investig, 17(1): 55–66.
30. Patil KS, Mahajani M (2022). Efficacy of 1.5% Metformin Gel as an Adjuvant to Scaling, Root Planing, and Curettage for the Treatment of Infrabony Defects in Chronic Periodontitis Patients. Contemp Clin Dent, 13(1): 18–23.
31. Pilloni A, Rojas MA (2023). Clinical effects of the adjunctive use of polynucleotide and hyaluronic acid-based gel in the subgingival re-instrumentation of residual periodontal pockets: A randomized, split-mouth clinical trial. J Periodontol, 94(3): 354–363.
32. Rassameemasmaung S, Sirikulsathean A (2008). Topical application of Garcinia mangostana L. pericarp gel as an adjunct to periodontal treatment. Complement Ther Med, 16(5): 262–267.
33. Rattanasuwan K, Rassameemasmaung S (2016). Clinical effect of locally delivered gel containing green tea extract as an adjunct to non-surgical periodontal treatment. Odontology, 104(1): 89–97.
34. Saberi BV, Radafshar G (2017). Effect of Topical Gel Chlorhexidine 0.2% on Non-Surgical Treatment of Chronic Periodontitis. J Babol Univ Med Sci, 19: 74-80.
35. Taalab MR, Mahmoud SA (2021). Intrapocket application of tea tree oil gel in the treatment of stage 2 periodontitis. BMC Oral Health, 21(1): 239.
36. Yaghini J, Shahabooei M (2014). Efficacy of a local-drug delivery gel containing extracts of Quercus brantii and Coriandrum sativum as an adjunct to scaling and root planing in moderate chronic periodontitis patients. J Res Pharm Pract, 3(2): 67–71.
37. Daly CG, Kieser J (1979). Cementum involved in periodontal disease: a review of its features and clinical management. J Dent, 7(3): 185–193.
38. Mombelli A, Nyman S (1995). Clinical and microbiological changes associated with an altered subgingival environment induced by periodontal pocket reduction. J Clin Periodontol, 22(10): 780–787.
39. Bogren A, Teles RP (2008). Locally delivered doxycycline during supportive periodontal therapy: a 3-year study. J Periodontol, 79(5): 827–835.
40. Rajeshwari HR, Dhamecha D (2019). Local drug delivery systems in the management of periodontitis: A scientific review. J Control Release, 307: 393–409.
41. Medellín-Castillo NA, Isaacs-Páez ED (2021). Formaldehyde and tripolyphosphate crosslinked chitosan hydrogels: Synthesis, characterization and modeling. Int J Biol Macromol, 183: 2293–2304.
42. Lou J, Stowers R (2018). Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture. Biomaterials, 154: 213–222.
43. Hemmingsen LM, Julin K (2021). Chitosomes-In-Chitosan Hydrogel for Acute Skin Injuries: Prevention and Infection Control. Mar Drugs, 19(5): 269.
44. Sagbas SS, Ari B (2019). Hyaluronic acid and hyaluronic acid: Sucrose nanogels for hydrophobic cancer drug delivery. Int J Biol Macromol, 126: 1150–1157.
45. Lecio G, Ribeiro FV (2020). Novel 20% doxycycline-loaded PLGA nanospheres as adjunctive therapy in chronic periodontitis in type-2 diabetics: randomized clinical, immune and microbiological trial. Clin Oral Investig, 24(3): 1269–1279.
46. Brooke ZLS, Belfield LA (2021). Effects of chlorhexidine mouthwash on the oral microbiome. J Dent, 113: 103768.
47. Azambuja JH, Mancuso RI (2022). Protective effect of green tea and epigallocatechin-3-gallate in a LPS-induced systemic inflammation model. J Nutr Biochem, 101: 108920.
48. Loos BG, Needleman I (2020). Endpoints of active periodontal therapy. J Clin Peri-odontol, 47 Suppl 22(Suppl 22):61-71.
2. Chen M, Cai W (2019). Oxidative stress-related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: A systematic review and meta-analysis. J Clin Periodontol, 46(6): 608–622.
3. Kavarthapu A, Gurumoorthy K (2021). Linking chronic periodontitis and oral cancer: A review. Oral Oncol, 121: 105375.
4. Wang RP, Ho YS (2019). Systemic inflammation linking chronic periodontitis to cognitive decline. Brain Behav Immun, 81: 63–73.
5. Sayed EN, Baeumer A (2019). Twenty years later: Oral health-related quality of life and standard of treatment in patients with chronic periodontitis. J Periodontol, 90(4): 323–330.
6. Ilango P, Mahendra J (2021). Evidence linking the role of periodontal viruses in coronary artery disease with and without periodontitis. J Periodontol, 92(1): 113–122.
7. Takeguchi A, Miyazawa, K (2021). Effects of a β2-adrenergic receptor blocker on experimental periodontitis in spontaneously hypertensive rats. Life Sci, 277: 119593.
8. Choi S, Kim K (2019). Association of Chronic Periodontitis on Alzheimer's Disease or Vascular Dementia. J Am Geriatr Soc, 67(6): 1234–1239.
9. Fleury V, Zekeridou A (2021). Oral Dysbiosis and Inflammation in Parkinson's Disease . J Parkinsons Dis, 11(2): 619-31.
10. Zhao X, Yang Y (2022). Injectable hydrogels with high drug loading through B-N coordination and ROS-triggered drug release for efficient treatment of chronic periodontitis in diabetic rats. Biomaterials, 282: 121387.
11. AlSakr A, Blanchard S (2021). Association between intracranial carotid artery calcifications and periodontitis: A cone-beam computed tomography study. J Periodontol, 92(10): 1402–1409.
12. Liu M, Liu Q (2021). LncRNA LTSCCAT promotes tongue squamous cell carcinoma metastasis via targeting the miR-103a-2-5p/SMYD3/TWIST1 axis. Cell Death Dis, 12(2): 144.
13. Yao Y, Shen X (2021). Periodontal Pathogens Promote Oral Squamous Cell Carcinoma by Regulating ATR and NLRP3 Inflammasome. Front Oncol, 11: 722797.
14. D'Aiuto F, Gkranias N (2018). Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial. Lancet Diabetes Endocrinol, 6(12): 954–965.
15. Kaku M, Matsuda S (2021). Generalized periodontitis treated with periodontal, orthodontic, and prosthodontic therapy: A case report. World J Clin Cases, 9(21): 6110–6124.
16. Fang F, Gao B (2021). Efficacy of root canal therapy combined with basic periodontal therapy and its impact on inflammatory responses in patients with combined periodontal-endodontic lesions. Am J Transl Res, 13(12): 14149–14156.
17. Cecoro G, Piccirillo A (2021). Efficacy of locally delivered statins as an adjunct to scaling and root planning in the treatment of periodontitis: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci, 25(18): 5737–5754.
18. Pretzl B, Sälzer S (2019). Administration of systemic antibiotics during non-surgical periodontal therapy-a consensus report. Clin Oral Investig, 23(7): 3073–3085.
19. Almoshari Y, Ren R (2020). GSK3 inhibitor-loaded osteotropic Pluronic hydrogel effectively mitigates periodontal tissue damage associated with experimental periodontitis. Biomaterials, 261: 120293.
20. Naga K, Ideguchi H (2020). An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during resolution of experimental periodontitis. FASEB J, 34(10): 13726–13740.
21. Gupta R, Pandit N (2008). Comparative evaluation of subgingivally delivered 10% doxycycline hyclate and xanthan-based chlorhexidine gels in the treatment of chronic periodontitis. J Contemp Dent Pract, 9(7): 25–32.
22. Ilyes I, Rusu D (2023). A Placebo-Controlled Trial to Evaluate Two Locally Delivered Antibiotic Gels (Piperacillin Plus Tazobactam vs. Doxycycline) in Stage III-IV Periodontitis Patients. Medicina (Kaunas), 59(2): 303.
23. Flemmig TF, Petersilka G (2011). Efficacy and safety of adjunctive local moxifloxacin delivery in the treatment of periodontitis. J Periodontol, 82(1): 96–105.
24. Radulescu V, Boariu MI (2022). Clinical and microbiological effects of a single application of sodium hypochlorite gel during subgingival re-instrumentation: a triple-blind randomized placebo-controlled clinical trial. Clin Oral Investig, 26(11): 6639–6652.
25. Liang FZ, Wang JL (2020). Effect of ultrasonic subgingival scaling combined with hyaluronic acid gel treatment on the efficacy of periodontitis and the expression of CRP and VEGF in the elderly. Chinese Journal of Gerontology, 40(19): 4146-4149.
26. Dong ZH, Shi SG (2012). Application of slow-release chlorhexidine gel in the treatment of chronic periodontitis. Journal of Endodontics and Periodontology. 22(10): 594-6.
27. Kadadasu R, Atchuta A (2020). Clinicomicrobiological evaluation of the efficacy of local delivery of moxifloxacin and ibuprofen gel as an adjunct to scaling and root planing in chronic periodontitis patients. J Oral Maxillofac Pathol, 24(1): 26–32.
28. Mahendra J, Mahendra L (2013). Clinical effects of subgingivally delivered spirulina gel in chronic periodontitis cases: a placebo controlled clinical trial. J Clin Diagn Res, 7(10): 2330–2333.
29. Matesanz P, Herrera D (2013). A randomized clinical trial on the clinical and microbiological efficacy of a xanthan gel with chlorhexidine for subgingival use. Clin Oral Investig, 17(1): 55–66.
30. Patil KS, Mahajani M (2022). Efficacy of 1.5% Metformin Gel as an Adjuvant to Scaling, Root Planing, and Curettage for the Treatment of Infrabony Defects in Chronic Periodontitis Patients. Contemp Clin Dent, 13(1): 18–23.
31. Pilloni A, Rojas MA (2023). Clinical effects of the adjunctive use of polynucleotide and hyaluronic acid-based gel in the subgingival re-instrumentation of residual periodontal pockets: A randomized, split-mouth clinical trial. J Periodontol, 94(3): 354–363.
32. Rassameemasmaung S, Sirikulsathean A (2008). Topical application of Garcinia mangostana L. pericarp gel as an adjunct to periodontal treatment. Complement Ther Med, 16(5): 262–267.
33. Rattanasuwan K, Rassameemasmaung S (2016). Clinical effect of locally delivered gel containing green tea extract as an adjunct to non-surgical periodontal treatment. Odontology, 104(1): 89–97.
34. Saberi BV, Radafshar G (2017). Effect of Topical Gel Chlorhexidine 0.2% on Non-Surgical Treatment of Chronic Periodontitis. J Babol Univ Med Sci, 19: 74-80.
35. Taalab MR, Mahmoud SA (2021). Intrapocket application of tea tree oil gel in the treatment of stage 2 periodontitis. BMC Oral Health, 21(1): 239.
36. Yaghini J, Shahabooei M (2014). Efficacy of a local-drug delivery gel containing extracts of Quercus brantii and Coriandrum sativum as an adjunct to scaling and root planing in moderate chronic periodontitis patients. J Res Pharm Pract, 3(2): 67–71.
37. Daly CG, Kieser J (1979). Cementum involved in periodontal disease: a review of its features and clinical management. J Dent, 7(3): 185–193.
38. Mombelli A, Nyman S (1995). Clinical and microbiological changes associated with an altered subgingival environment induced by periodontal pocket reduction. J Clin Periodontol, 22(10): 780–787.
39. Bogren A, Teles RP (2008). Locally delivered doxycycline during supportive periodontal therapy: a 3-year study. J Periodontol, 79(5): 827–835.
40. Rajeshwari HR, Dhamecha D (2019). Local drug delivery systems in the management of periodontitis: A scientific review. J Control Release, 307: 393–409.
41. Medellín-Castillo NA, Isaacs-Páez ED (2021). Formaldehyde and tripolyphosphate crosslinked chitosan hydrogels: Synthesis, characterization and modeling. Int J Biol Macromol, 183: 2293–2304.
42. Lou J, Stowers R (2018). Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture. Biomaterials, 154: 213–222.
43. Hemmingsen LM, Julin K (2021). Chitosomes-In-Chitosan Hydrogel for Acute Skin Injuries: Prevention and Infection Control. Mar Drugs, 19(5): 269.
44. Sagbas SS, Ari B (2019). Hyaluronic acid and hyaluronic acid: Sucrose nanogels for hydrophobic cancer drug delivery. Int J Biol Macromol, 126: 1150–1157.
45. Lecio G, Ribeiro FV (2020). Novel 20% doxycycline-loaded PLGA nanospheres as adjunctive therapy in chronic periodontitis in type-2 diabetics: randomized clinical, immune and microbiological trial. Clin Oral Investig, 24(3): 1269–1279.
46. Brooke ZLS, Belfield LA (2021). Effects of chlorhexidine mouthwash on the oral microbiome. J Dent, 113: 103768.
47. Azambuja JH, Mancuso RI (2022). Protective effect of green tea and epigallocatechin-3-gallate in a LPS-induced systemic inflammation model. J Nutr Biochem, 101: 108920.
48. Loos BG, Needleman I (2020). Endpoints of active periodontal therapy. J Clin Peri-odontol, 47 Suppl 22(Suppl 22):61-71.
| Files | ||
| Issue | Vol 53 No 6 (2024) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i6.15898 | |
| Keywords | ||
| Chronic periodontitis Meta-analysis Drug-loaded gel Adjunctive drug therapy Efficacy evaluation | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Li Z, Yang X, Wang J, Qin Z, Meng Y, Zhang B. Adjunctive Drug-Loaded Gel in the Treatment of Periodontitis: A Systematic Evaluation and Meta-Analysis. Iran J Public Health. 2024;53(6):1246-1260.
