Clinical and Radiographic Evaluation of Doxycycline and Atorvastatin Loaded Chitosan Nanoparticles as an Adjunctive to Scaling and Root Planning in the Management of Chronic Periodontitis. A Randomized Controlled Clinical Trial.

Official title

Clinical and Radiographic Evaluation of Doxycycline and Atorvastatin Loaded Chitosan Nanoparticles as an Adjunctive to Scaling and Root Planning in the Management of Chronic Periodontitis: A Randomized Controlled Clinical Trial.

Overview

Chronic periodontitis is one of the most prevalent inflammatory diseases affecting the tooth-supporting structures and is characterized by progressive clinical attachment loss and alveolar bone resorption resulting from a complex interaction between pathogenic microorganisms and the host inflammatory and immune responses. If left untreated, the disease may ultimately lead to tooth loss and negatively affect oral health and quality of life. Scaling and root planing (SRP) is considered the gold-standard non-surgical treatment for chronic periodontitis. It aims to remove dental plaque and calculus deposits and reduce the subgingival bacterial load. Although SRP has demonstrated significant clinical benefits, its effectiveness may be limited in certain situations, particularly in deep periodontal pockets and anatomically complex areas that are difficult to access. Therefore, adjunctive therapeutic approaches have been investigated to enhance treatment outcomes and improve long-term periodontal stability. In recent years, local drug delivery systems have gained considerable attention in periodontal therapy due to their ability to provide high therapeutic concentrations directly at the site of infection while minimizing systemic adverse effects. Chitosan has emerged as a promising biomaterial for this purpose because of its excellent biocompatibility, biodegradability, antimicrobial properties, and its ability to form nanoparticles capable of sustained and controlled drug release within periodontal pockets. Doxycycline is widely used in periodontal treatment because of its antimicrobial activity against periodontal pathogens as well as its ability to inhibit matrix metalloproteinases (MMPs), which play a key role in connective tissue destruction and alveolar bone loss. Furthermore, recent studies have demonstrated that atorvastatin, beyond its well-known lipid-lowering effects, possesses anti-inflammatory, immunomodulatory, and osteogenic properties that may contribute to periodontal tissue regeneration and improved clinical outcomes. The research problem arises from the limited effectiveness of scaling and root planing alone in some cases of chronic periodontitis and the need for innovative adjunctive therapies that combine antimicrobial, anti-inflammatory, and bone regenerative effects. Therefore, evaluating the therapeutic potential of chitosan nanoparticles loaded with doxycycline and atorvastatin may provide a novel and effective approach for periodontal treatment. The aim of this study is to clinically and radiographically evaluate the effectiveness of chitosan nanoparticles loaded with doxycycline and atorvastatin as an adjunct to scaling and root planing in patients with chronic periodontitis. Clinical outcomes, including probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP), as well as radiographic changes in alveolar bone levels, will be assessed and compared with conventional treatment outcomes. The findings of this study may contribute to the development of a more effective and biologically targeted therapeutic strategy for the management of chronic periodontitis.

Detailed description

Chronic periodontitis is one of the most prevalent inflammatory diseases affecting the tooth-supporting structures and is characterized by progressive clinical attachment loss and alveolar bone resorption resulting from a complex interaction between pathogenic microorganisms and the host inflammatory and immune responses. If left untreated, the disease may ultimately lead to tooth loss and negatively affect oral health and quality of life.

Scaling and root planing (SRP) is considered the gold-standard non-surgical treatment for chronic periodontitis. It aims to remove dental plaque and calculus deposits and reduce the subgingival bacterial load. Although SRP has demonstrated significant clinical benefits, its effectiveness may be limited in certain situations, particularly in deep periodontal pockets and anatomically complex areas that are difficult to access. Therefore, adjunctive therapeutic approaches have been investigated to enhance treatment outcomes and improve long-term periodontal stability.

In recent years, local drug delivery systems have gained considerable attention in periodontal therapy due to their ability to provide high therapeutic concentrations directly at the site of infection while minimizing systemic adverse effects. Chitosan has emerged as a promising biomaterial for this purpose because of its excellent biocompatibility, biodegradability, antimicrobial properties, and its ability to form nanoparticles capable of sustained and controlled drug release within periodontal pockets.

Doxycycline is widely used in periodontal treatment because of its antimicrobial activity against periodontal pathogens as well as its ability to inhibit matrix metalloproteinases (MMPs), which play a key role in connective tissue destruction and alveolar bone loss. Furthermore, recent studies have demonstrated that atorvastatin, beyond its well-known lipid-lowering effects, possesses anti-inflammatory, immunomodulatory, and osteogenic properties that may contribute to periodontal tissue regeneration and improved clinical outcomes.

The research problem arises from the limited effectiveness of scaling and root planing alone in some cases of chronic periodontitis and the need for innovative adjunctive therapies that combine antimicrobial, anti-inflammatory, and bone regenerative effects. Therefore, evaluating the therapeutic potential of chitosan nanoparticles loaded with doxycycline and atorvastatin may provide a novel and effective approach for periodontal treatment.

The aim of this study is to clinically and radiographically evaluate the effectiveness of chitosan nanoparticles loaded with doxycycline and atorvastatin as an adjunct to scaling and root planing in patients with chronic periodontitis. Clinical outcomes, including probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP), as well as radiographic changes in alveolar bone levels, will be assessed and compared with conventional treatment outcomes. The findings of this study may contribute to the development of a more effective and biologically targeted therapeutic strategy for the management of chronic periodontitis.

Interventions

• Drug Doxycycline and Atorvastatin loaded Chitosan nanoparticles local drug
  the group will receive the local drug using a blunt cannula syringe (26 gauge), injecting 0.1 mL of the prepared drug gel into the periodontal pocket (one per patient). After delivery, the gel will become more viscous and occluded the pockets, thus eliminating the need for placing periodontal dressing. After LDD, patients will be instructed to avoid chewing on sticky/hard foodstuff or using toothbrush/interdental aids near the treated areas for 1 week. All patients will receive the same postoper

Primary outcome measures

• Reduction in periodontal parameters [Time frame: From enrollment to the end of treatment at 6 months]

Secondary outcome measures (4)

• Reduction in bleeding on probing [Time frame: from enrollment to 6 months]
• Reduction in gingival index [Time frame: from enrollment to 6 months]
• Reduction in plaque index [Time frame: from enrollment to 6 months]
• Radiographic improvement : [Time frame: from enrollment to 6 months]

Eligibility criteria

Inclusion criteria

• In order for patients to be considered in the study, they must meet the following criteria: 1) they should have stage II and stage III periodontitis 2) Patients' age range equal or more than 25 years old .

Exclusion criteria

\- Patients with any systemic condition that may affect periodontal health and bone formation, such as; those who are pregnant, nursing, or postmenopausal women; DM, CVD, metabolic syndrome, osteoporosis, AIDS and chronic alcoholism .

2\) Patients having local factors that may aggravate and predispose for periodontal diseases such as; orthodontic and prosthetic appliances and parafunctional habits 3)smoking (A patient was classified as a current smoker if they smoked more than 10 cigarettes per day regularly for a minimum period of 5 years) 4) Individuals on systemic drug affecting metabolic bone diseases , Medications taken for the treatment of arthritis and psychotropic and epileptic disorders, as well as anticoagulants, antacids, bisphosphonates, corticosteroids, and antineoplastic drugs, can profoundly affect bone metabolism

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Fayoum — Al Fayyum

Publications

• Calvo P, Remunan-Lopez C, Vila-Jato JL, Alonso MJ. Chitosan and chitosan/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines. Pharm Res. 1997 Oct;14(10):1431-6. doi: 10.1023/a:1012128907225. PMID 9358557
• Goodman SB, Jiranek W, Petrow E, Yasko AW. The effects of medications on bone. J Am Acad Orthop Surg. 2007 Aug;15(8):450-60. doi: 10.5435/00124635-200708000-00002. PMID 17664365
• Nicotine involved in periodontal disease through influence on cytokine profile in gingival crevicular fluid. Kamma, J. J., Giannopoulou, C., Vasdekis, V. G., & Mombelli, A. (2004). FEMS Immunology & Medical Microbiology, 52(2), 282-290. https://doi.org/10.1016/j.femspd.2004.03.008
• Alfuriji S, Alhazmi N, Alhamlan N, Al-Ehaideb A, Alruwaithi M, Alkatheeri N, Geevarghese A. The effect of orthodontic therapy on periodontal health: a review of the literature. Int J Dent. 2014;2014:585048. doi: 10.1155/2014/585048. Epub 2014 May 29. PMID 24991214
• Albandar JM. Global risk factors and risk indicators for periodontal diseases. Periodontol 2000. 2002;29:177-206. doi: 10.1034/j.1600-0757.2002.290109.x. No abstract available. PMID 12102708
• Ashokan DB, Shekar MK, Dharani K, Mani E, Pampani P, Ravichandran B. Clinical evaluation of photobiomodulation therapy and local 1.2% atorvastatin gel as an adjunct to subgingival instrumentation in patients with stage II periodontitis: a randomized controlled trial. Quintessence Int. 2025 Jul 21;56(7):514-527. doi: 10.3290/j.qi.b6218534. PMID 40377185
• Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Clin Periodontol. 2018 Jun;45 Suppl 20:S149-S161. doi: 10.1111/jcpe.12945. PMID 29926495
• Yıldırım, Y., Kaya, S., & Demirci, T. (2023). Doxycycline- and atorvastatin-loaded chitosan nanoparticles as a local drug delivery system for periodontitis therapy: In vitro evaluation of antimicrobial activity and release profile. Journal of Drug Delivery Science and Technology, 78, 104145. https://doi.org/10.1016/j.jddst.2023.104145

Identifiers

NCT: NCT07634341 · FAY-DC,AV LOADED CS PERIO RCT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗