Clinical and microbiological evaluation of four different local drug delivery agents in the management of stage I Grade A/B Periodontitis: A Comparative Study

International Journal of Dental Science and Innovative Research (IJDSIR) IJDSIR : Dental Publication Service Available Online at:www.ijdsir.com Volume – 8, Issue – 4, August – 2025, Page No. : 297 - 309 Corresponding Author: Dr Navneet Kaur, ijdsir, Volume – 8 Issue - 4, Page No. : 297 - 309 Page297 ISSN: 2581-5989 PubMed - National Library of Medicine - ID: 101738774 Clinical and microbiological evaluation of four different local drug delivery agents in the management of stage I Grade A/B Periodontitis: A Comparative Study 1Dr Navneet Kaur, PhD Scholar, Department of Periodontology & Oral Implantology, Desh Bhagat University, Mandi, Gobindgarh. Punjab. 2Dr Vikram Bali, Professor & Head, Department of Periodontology & Oral Implantology, Desh Bhagat University, Mandi, Gobindgarh. 3Dr Vaneet Gupta, Associate Professor, Department of Periodontology & Oral Implantology, Yamuna Institute of Dental Sciences & Research, Yamuna Nagar, Haryana. Corresponding Author: Dr Navneet Kaur, PhD Scholar, Department of Periodontology & Oral Implantology, Desh Bhagat University, Mandi, Gobindgarh. Punjab. Citation of this Article: Dr Navneet Kaur, Dr Vikram Bali, Dr Vaneet Gupta, “Clinical and microbiological evaluation of four different local drug delivery agents in the management of stage I Grade A/B Periodontitis: A Comparative Study”, IJDSIRAugust – 2025, Volume – 8, Issue – 4, P. No. 297 – 309. Copyright: © 2025, Dr Navneet Kaur, et al. This is an open access journal and article distributed under the terms of the creative common’s attribution non-commercial License. Which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given, and the new creations are licensed under the identical terms. Type of Publication: Original Research Article Conflicts of Interest: Nil Abstract Background: Periodontitis is a complex multifactorial disease and results in a progressive loss of attachment and formation of periodontal pocket. There are multiple options of anti-microbials that can be locally delivered into the mucosa such as Tetracycline, Doxycycline, Silver nanoparticle Chlorhexidine, Metronidazole, Ornidazole and Quaternary ammonium compounds. Since research with drug delivery system is limited, this clinical study evaluates the comparative efficacy of four different local drug delivery agents as an adjunct to scaling and root planing in the management of Stage I Grade A/B periodontitis. Material and Methods: The study involved 140 patients randomly divided into 4 groups/sites. Group 1/Site 1 treated with Ornidazole as an adjunct to SRP, Group 2/Site 2 treated with Metronidazole as an adjunct to SRP, Group 3/Site 3 treated with Siver nanoparticle gel as an adjunct to SRP and Group 4/Site 4 treated with oxygen releasing formula blue M gel as an adjunct to SRP. Clinical parameters were assessed for investigation included PI, GI, PPD and CAL at baseline, 1 month and 3 months. Microbiological parameters were recorded following baseline and after 3 months for every subject in all the four groups post treatment. Results: All the groups showed significant improvement in PI, GI, PPD and CAL gain from baseline to 3 months of time interval when treated with Ornidazole, Metronidazole, Siver nanoparticle gel and oxygen releasing formula blue M gel. Group 4/Site 4 and Group Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 Page298 3/Sites 3 showed more substantial reductions in CFU counts 4.30×102±6.11 and 3.67×102±4.72 respectively after 3 months of intervention. Conclusion: It can be assumed that the adjunctive use of oxygen releasing formula (Blue M gelTM), Siver nanoparticle gel (Megaheal gelTM), Ornidazole (Ornigreat gelTM) and Metronidazole (Metrohex plus gelTM) after scaling and root planning improved the treatment outcome in subjects with Stage I Grade A/B periodontitis. Keywords: Periodontitis, adjunctive treatment, Ornidazole, Metronidazole, Siver nanoparticle gel, oxygen releasing formula blue M gel, anaerobic flora, bacterial count Introduction Periodontitis is a chronic inflammatory condition affecting the tooth-supporting structures, leading to progressive damage of the periodontal ligament and alveolar bone. The disease is initiated by specific bacteria residing in the subgingival biofilm and is exacerbated by the host’s immune-inflammatory response to these pathogens. The sub gingival biofilm harbour’s a variety of bacterial species; the composition of the biofilm may vary between subjects and sites. Among the various Gram-negative anaerobic species associated with periodontitis, Porphyromonas gingivalis is recognized as a primary causative organism.1,2 It includes the initial microbial challenge, a subsequent host inflammatory response, and various risk factors that contribute to host susceptibility and progression of the disease. Management of periodontitis focuses on eliminating microbial etiologic factors and restoring periodontal health. Treatment approaches include patient education on oral hygiene, non-surgical interventions, surgical procedures, and ongoing supportive periodontal therapy. Mechanical debridement and the quality of the patient’s home care are of vital importance in preventing inflammation that manifests as both gingivitis and periodontitis. Scaling and root planing (SRP) remains the gold standard for non-surgical care, traditionally performed with hand instruments or ultrasonic scalers. This therapy leads to significant improvements in subgingival microbial composition and clinical parameters.3 However, conventional SRP may be less effective in certain situations, such as when treating inaccessible deep pockets, furcation areas, or root concavities, or when systemic health issues impair the host’s immune response. In such cases, adjunctive measures—such as systemic antibiotics, sub gingival irrigation and locally delivered antimicrobial agents are often employed alongside SRP. Local drug delivery agents used locally into the periodontal pocket with advantage of positive results in periodontitis cases. However, the flaw for systemic antibiotics allergic reactions, resistance to microflora, time period of action is slow and deficient and in some cases GIT disturbances. To overthrow the problems with systemic antibiotics local drug delivery agents was introduced by Goodson’s et al in 1979 in various forms such as fibers, films, gels, vesicles, strips and nanoparticle systems. The resorbable carriers are used locally in the form of tetracycline, minocycline, metronidazole, doxycycline, ornidazole and silver nanoparticle gel etc. as an additional therapy with mechanical scaling and root planning.4,5 Local drug delivery agents can be released in controlled manner or sustained release and follows zero order and first order kinetics respectively.6 Ornidazole is a safe, reliable controlled-release of local drug delivery agent. It contains 0.25% chlorhexidine gluconate w/w + 1% ornidazole w/w. It has a direct Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 Page299 interaction with the genetic material DNA causes suppression of protein synthesis and cell death. The biodegradable controlled delivery methods of ornidazole follows zero order kinetic and has low minimal inhibitory concentration. Metronidazole is a semi solid suspension broadly effective against anaerobic microflora like Fusobacterium, P. gingivalis, P. intermedia, spirochetes and clostridium species.7,8 Having a semi solid suspension, the drug remains in the periodontal pocket without the flushing action of GCF. Recent advancement in nanotechnology introduced a new therapeutic material is silver nanoparticle gel. The gel has a bacteriostatic action based on three principal mechanisms: firstly, interaction with DNA genetic material, secondly cell membrane destruction and thirdly blocked the enzymes which are important for regulation of transport of electrons.9 Silver is the metal of choice as they hold the promise to kill microbes effectively. Silver nanoparticles have been recently known to be a promising antimicrobial agent that acts on a broad range of target sites both extracellularly as well as intracellularly. Silver nanoparticles are effective against gram positive as well as gram negative bacteria including multi-resistant strains. Oxygen releasing formula gel which is blue M gel is composed of sodium perborate, Xylitol, Lactoferrin and glucose oxidase enzyme derived from honey. The high proportion of active oxygen concentration reduces pocket depth, bleeding gums, and wound healing. The distinctive formula improves oral hygiene of an individual and also reduces the risk of infections and inflammation.10 Blue m gel has the property of anti-plaque and anti-gingivitis when used topically in the oral cavity however the literature data is very limited for oxygen therapy as topical approach. In the light of the above facts, the aim of the present study is the comparative evaluation of four different local delivery agents as an adjunct to scaling and root planning in the management of Stage I Grade A/B periodontitis. Materials and Methodology Study Population For the proposed study, a total of 140 patients diagnosed with Stage I Grade A/B periodontitis having minimum of 5 teeth with PPD between 5-6 mm were selected from the outpatient department of Periodontics and Oral Implantology Desh Bhagat dental college & hospital. An ethical approval for the study was obtained from the Institutional Ethical Board Committee and a detailed verbal and written consent was taken from each of the patient. Randomized control clinical trial was performed. Patients were allocated randomly into four study groups/sites. Group 1 / Site 1comprised of 35 patients treated with Ornidazole (Ornigreat gelTM) as additional therapy to SRP. Group 2 / Site 2 – comprised of 35 patients treated with Metronidazole (Metrohex plus gelTM) as additional therapy to SRP. Group 3 / Site 3comprised of 35 patients treated with Siver nanoparticle gel (Megaheal gelTM) as additional therapy to SRP. Group 4 / Site 4comprised of 35 patients treated with oxygen releasing formula (Blue M gelTM) as additional therapy to SRP. Inclusion Criteria  Patient should have minimum of 20 teeth  Patient of both genders between age group 20-50 years  Patients diagnosed with Stage I Grade A/B periodontitis having minimum of 5 teeth with PPD between 5-6 mm  Patient had not experienced any periodontal therapy from past 6 months Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300 Page300  Patient freed from any unusual oral lesion.  Patients had not experienced any antibiotic therapy from past 6 months  Systemically healthy patient without known allergic conditions Exclusion Criteria  Patients with known allergy to metronidazole, chlorhexidine, silver nanoparticles or ornidazole  Patient with systemic disease  Smoker and Chronic alcoholic patients  Any tooth with periapical disease  Teeth with furcation involvement  Pregnancy, lactation and use of contraceptives medication Methodology A total of 140 patients diagnosed with Stage I Grade A/B periodontitis having minimum of 5 teeth with PPD between 5-6 mm were selected& divided into four groups/sites with 35 patients in each group/site. A thorough phase I therapy was conducted that encompassing patient guidance and activation as well as plaque control measures. All patients were instructed to follow oral hygiene measures that include tooth brushing with a soft brush two times a day. Group 1 / Site 135 patients received subgingival administration of Ornidazole (Ornigreat Gel™) as part of the treatment protocol into the deepest selected periodontal pocket using a disposable syringe. The drug was delivered by blunting the cannula tip to keep down the chance for tissue trauma. After isolating and drying the target site, the gel was carefully dispensed into the base of the periodontal pocket. A periodontal dressing was subsequently placed over the site to secure the area. Group 2 / Site 2 – 35 patients received subgingival delivery of Metronidazole (Metrohex Plus Gel™) into the deepest selected periodontal pocket using disposable syringe. The procedure was performed by dulling the cannula tip to prevent damage of tissue by sharp needle. After isolating and drying the treatment site, the gel was carefully introduced into the base of the periodontal pocket. A periodontal dressing was subsequently applied to protect the area. Group 3 / Site 335 patients received subgingival application of silver nanoparticle gel (Megaheal Gel™) into the deepest selected periodontal pocket using disposable syringe. The disposable syringe was prepared by blunting the cannula tip to prevent any potential tissue injury that could occur with a sharp needle. After proper isolation and drying of the treatment site, the gel was carefully dispensed into the base of the periodontal pocket. A periodontal dressing was applied afterward to secure and protect the area. Group 4 / Site 435 patients received subgingival application of an oxygen-releasing formulation (Blue M Gel™) into the deepest selected periodontal pocket using disposable syringe. The disposable syringe was prepared by dulling the tip of the cannula to prevent potential trauma to the soft tissues. The site was isolated and dried before carefully introducing the gel into the base of the periodontal pocket. Periodontal dressing utilized to protect and stabilize the area. Postoperative directions for home included soft bristle tooth brush two times daily without utilizing chemotherapeutics and irrigation devices was discouraged. Subgingival Plaque Sample Collection Plaque samples below the gingival margin gathered at baseline and after three months using sterile paper points. The sample was put down directly into sterile glass vial composed of 2.5 ml as fluid thioglycolate medium and transported to the Microbiology Department for anaerobic bacterial analysis. The resulting suspension Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 Page301 was subjected to serial dilution using the same medium to achieve a final dilution factor of 10². From each dilution, 0.1 ml was injected on plate of blood agar and evenly spread using a sterile glass spreader following the spread plate technique. The culture media employed included blood agar enriched with 5–10% fresh sheep or human blood and nutrient agar supplemented with 5–10% defibrinated fresh blood. The injected plate laid down under anaerobic conditions using an anaerobic jar equipped with a GasPak system, maintained at 37°C for 48 to 72 hours. Upon completion of incubation, plate was inspected to check growth of bacteria in the form of colonies. The total colony count on each plate was recorded, and bacterial concentration manifested as colony-forming units per millilitre (cfu/ml) using the standard formula: Assessment of Clinical and Microbiological Parameter Clinical parameters were assessed for investigation included Plaque index, Gingival index, Probing Pocket depth and Clinical attachment level (with the help of UNC-15 Probe). These variables were assessed at baseline, 1 month and 3 months. Microbiological parameters were recorded following baseline and after 3 months for every subject in all the four groups post treatment. Statistical Analysis Numerical values were tabulated and analysed through Statistical Package SPSS 23.0 version. Descriptive statistics for variable with numerical values collected was carried out. The descriptive statistics included mean, standard deviation frequency and percentage Different parameter were compared through One-way analysis of variance (ANOVA), Bonferroni post hoc ANOVA and Paired t test for intergroup and intragroup comparison. Results Table 1: Intergroup comparison of all clinical parameters among different groups within different time period Time Period Group/Site Plaque Index (PI) Gingival Index (GI) Probing Pocket Depth (PPD) Clinical Attachment Level (CAL) Mean±SD p value Mean±SD p value Mean±SD p value Mean±SD p value At Baseline Group 1/site 1 1.88±0.31 0.012* 2.12±0.27 0.020* 5.55±0.39 0.079** 7.54±0.39 0.316** Group 2/site 2 2.01±0.23 2.33±0.25 5.68±0.31 7.62±0.33 Group 3/site 3 1.83±0.36 2.15±0.39 5.73±0.25 7.47±0.38 Group 4/site 4 2.04±0.33 2.25±0.31 5.69±0.28 7.60±0.37 1 Month Group 1/site 1 1.26±0.35 0.072* * 1.62±0.31 0.001* 4.61±0.53 0.345** 6.66±0.38 0.902** Group 2/site 2 1.44±0.39 1.43±0.36 4.66±0.41 6.58±0.48 Group 3/site 3 1.47±0.38 1.39±0.39 4.82±0.59 6.62±0.53 Group 4/site 4 1.29±0.50 1.28±0.40 4.66±0.56 6.62±0.50 3 Months Group 1/site 1 1.08±0.29 0.029* 0.81±0.26 0.309** 3.54±0.56 0.269** 5.80±0.50 0.117** Group 2/site 2 1.13±0.30 0.76±0.35 3.57±0.56 5.60±0.55 Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Page302 Group 3/site 3 1.12±0.30 0.85±0.28 3.71±0.52 5.56±0.46 Group 4/site 4 0.96±0.16 0.73±0.27 3.46±0.56 5.53±0.53 * Statistically significant; ** statistically non-significant Table 1 showed intergroup comparison of all the clinical parameter was compared among different groups within different time period. The mean plaque index score at the baseline, 1 month and 3-month time interval were 1.88±0.31, 1.26±0.35 and 1.08±0.29 for the Group 1/Site 1. For the Group 2/Site 2, it was 2.01±0.23, 1.44 ±0.39 and 1.13±0.30 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 3/Site 3, it was 1.83±0.36, 1.47 ±0.38 and 1.12±0.30 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 4/Site 4, it was 2.04±0.33, 1.29±0.50 and 0.96±0.16 at the baseline, 1 month and 3 months’ time interval respectively. At baseline and after 3 months of time interval, the mean plaque index score was found to be statistically significant. However, it was found to be statistically non-significant after 1 month of time interval. The mean gingival index score at the baseline, 1 month and 3-month time interval were 2.12±0.27, 1.62±0.31 and 0.81±0.26 for the Group 1/Site 1. For the Group 2/Site 2, it was 2.33±0.25, 1.43±0.36 and 0.76±0.35 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 3/Site 3, it was 2.15±0.39, 1.39±0.39 and 0.85±0.28 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 4/Site 4, it was 2.25±0.31, 1.28±0.40 and 0.73±0.27 at the baseline, 1 month and 3 months’ time interval respectively. At baseline and after 1 month of time interval the mean gingival index score was found to be statistically significant. However, it was found to be statistically non-significant after 3 months of time interval. The mean probing pocket depth value at the baseline, 1 month and 3-month time interval were 5.55±0.39, 4.61±0.53 and 3.54±0.56 for the Group 1/Site 1. For the Group 2/Site 2, it was 5.68±0.31, 4.66±0.41 and 3.57±0.56 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 3/Site 3, it was 5.73±0.25, 4.82±0.59 and 3.71±0.52 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 4/Site 4, it was 5.69±0.28, 4.66±0.56 and 3.46±0.56 at the baseline, 1 month and 3 months’ time interval respectively. At baseline, after 1 month and after 3 months of time interval, probing pocket depth was found to be statistically non-significant. The mean clinical attachment level at the baseline, 1 month and 3-month time interval were 7.54±0.39, 6.66±0.38 and 5.80±0.50 for the group 1/site 1. For the group 2/site 2, it was 7.62±0.33, 6.58±0.48 and 5.60±0.55 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 3/Site 3, it was 7.47±0.38, 6.62±0.53 and 5.56±0.46 at the baseline, 1 month and 3 months’ time interval respectively. For the Group 4/Site 4, it was 7.60±0.37, 6.62±0.50 and 5.53±0.53 at the baseline, 1 month and 3 months’ time interval respectively. At baseline, after 1 month and after 3 months of time interval, clinical attachment level was found to be statistically non-significant. Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Page303 Graph 1: Intergroup comparison of plaque index score among different groups within different time period Graph 2: Intergroup comparison of gingival index score among different groups within different time period 1.88 1.26 1.08 2.01 1.44 1.13 1.83 1.47 1.12 2.04 1.29 0.96 0.00 0.50 1.00 1.50 2.00 2.50 Baseline 1 months 3 months Plaque index Group-1 Group-2 Group-3 Group-4 2.12 1.62 0.81 2.33 1.43 0.76 2.15 1.39 0.85 2.25 1.28 0.73 0 0.5 1 1.5 2 2.5 Baseline 1 months 3 months Gingival index Group-1 Group-2 Group-3 Group-4 Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Page304 Graph 3: Intergroup comparison of probing pocket depth among different groups within different time period Graph 4: Intergroup comparison of clinical attachment level among different groups within different time period Table 2: Intergroup comparison of colony forming unit among different groups within different time period Group/Site Mean±SD P Value At Baseline Group 1/site 1 24.11×102±20.83 0.140** Group 2/site 2 30.67×102±25.49 5.55 4.61 3.54 5.68 4.66 3.57 5.73 4.82 3.71 5.69 4.66 3.46 0 1 2 3 4 5 6 7 Baseline 1 months 3 months Probing pocket depth Group-1 Group-2 Group-3 Group-4 7.54 6.66 5.80 7.62 6.58 5.60 7.47 6.62 5.56 7.60 6.62 5.53 0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 Baseline 1 months 3 months Clinical attachment level Group-1 Group-2 Group-3 Group-4 Dr Navneet Kaur, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Page305 Group 3/site 3 21.72×102±18.13 Group 4/site 4 20.09×102±14.75 3 Months Group 1/site 1 8.09×102±10.92 0.052** Group 2/site 2 6.33×102±6.00 Group 3/site 3 3.67×102±4.72 Group 4/site 4 4.30×102±6.11 ** statistically non-significant Graph 5: Intergroup comparison of colony Forming Unit (× 102) among different groups within different time period The mean of Colony Forming Unit at the baseline and 3month time interval were 24.11×102±20.83 and 8.09×102±0.50 for the group 1/Site 1. For group 2/Site 2, the CFU count was 30.67×102±25.49 and 6.33×102±6.00 at the baseline and 3 months’ time interval respectively. For the Group 3/Site 3, the CFU count was 21.72×102±18.13 and 3.67×102±4.72 at the baseline and 3 months’ time interval respectively. For the Group 4/Site 4, the CFU count was 20.09×102±14.75 and 4.30×102±6.11 at the baseline and 3 months’ time interval respectively. At baseline and after 3 months of time interval, Colony Forming Unit was found to be statistically non-significant. Discussion Non-surgical mechanical periodontal therapy serves as the primary and foundational approach in the management of periodontal infections. This conventional treatment typically involves mechanical removal of supraand subgingival deposits, complemented by patient education on effective self-performed oral hygiene practices. Nevertheless, subgingival scaling and root planing is a technically challenging procedure and may not consistently achieve complete elimination of 24.11 8.09 30.67 6.33 21.72 3.67 20.09 4.30 0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00 Baseline 3 months Colony Forming Unit Group-1 Group-2 Group-3 Group-4