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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 12
| Issue : 2 | Page : 65-72 |
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Comparative evaluation of three commercially available local drug delivery medicaments in the treatment of chronic periodontitis
Sumanpreet Kaur Shergill1, Ridhima Sood1, Ridhi Aggarwal1, Jyotsana Singh1, Ena Sharma1, Sanjeev Jain2
1 Department of Periodontology, Rayat Bahra Dental College and Hospital, Sahibzada Ajit Singh Nagar, India
2 Department of Periodontology, Guru Nanak Dev Dental College and Research Institute, Sunam, Punjab, India
| Date of Submission | 05-Apr-2022 |
| Date of Decision | 31-Aug-2022 |
| Date of Acceptance | 07-Oct-2022 |
| Date of Web Publication | 19-Dec-2022 |
Correspondence Address:
Dr. Sumanpreet Kaur Shergill
Near Gurudwara, Tapyana Sahib, Dangarh, Barnala - 148 105, Punjab
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijohs.ijohs_9_22
Aim: The purpose of the present study was to compare the efficacy of 1.5% chlorhexidine gel, 0.8% hyaluronic acid gel, and 10% doxycycline gel used as an adjunct to scaling and root planning (SRP) and SRP alone in the management of chronic periodontitis.
Materials and Methods: Sixteen patients in the age group of 3060 years suffering from chronic periodontitis were selected for the study and divided into four groups. In Group I, after SRP, chlorhexidine gel (chlosite) was inserted up to the base of the pocket. In Group II and III, doxycycline gel and hyaluronic acid gel, respectively, were inserted up to the base of the pocket after SRP, and Group IV was used as a control. The clinical parameters such as probing pocket depth (PPD), relative attachment level (RAL), and gingival index (GI) were recorded at baseline, 6 weeks, and 3 months.
Results: There was statistically highly significant improvement in all the clinical parameters at 6 weeks and 3 months when chlorhexidine, doxycycline, and hyaluronic acid gel were used as an adjunct to SRP. Chlosite group showed statistically significant improvement in PPD and RAL as compared to other groups. With regard to GI, Group I showed a statistically significant reduction when compared to Group III (hyaluronic acid group) and IV (control group). However, the reduction was not statistically significant when compared to Group II (doxycycline group). When doxycycline and hyaluronic acid gel were used as an adjunct to SRP, it resulted in greater improvement in clinical parameters as compared to SRP alone, but the results were not statistically significant. Results were comparable for both drugs.
Keywords: Chlorhexidine, chronic periodontitis, doxycycline, hyaluronic acid
How to cite this article:
Shergill SK, Sood R, Aggarwal R, Singh J, Sharma E, Jain S. Comparative evaluation of three commercially available local drug delivery medicaments in the treatment of chronic periodontitis. Int J Oral Health Sci 2022;12:65-72 |
How to cite this URL:
Shergill SK, Sood R, Aggarwal R, Singh J, Sharma E, Jain S. Comparative evaluation of three commercially available local drug delivery medicaments in the treatment of chronic periodontitis. Int J Oral Health Sci [serial online] 2022 [cited 2023 Jun 7];12:65-72. Available from: https://www.ijohsjournal.org/text.asp?2022/12/2/65/364232 |
| Introduction | |  |
Periodontitis is an infectious disease resulting in inflammation of the supporting tissues of the teeth, progressive attachment loss, bone loss, and formation of periodontal pockets. It is a chronic inflammatory condition characterized by acute episodes of periodontal destruction occurring in response to an elevated bacterial load in a susceptible host.[14] Periodontal pockets provide an ideal environment for the proliferation of bacterial species associated with the disease.[25] Decreasing the bacterial load may lead to improved clinical results and more predictable periodontal healing.
The microbiota responsible for periodontal diseases is complex since more than 500 different species have been identified in subgingival plaque. The predominant microorganisms to colonize the gingival crevice include obligate anaerobic Gram-negative species such as Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythus, Fusobacterium nucleatum, Selenomonas, and Campylobacter species and facultative anaerobic Gram-negative rods such as Aggregatibacter actinomycetemcomitans, Capnocytophaga species, and Eikenella corrodens.[2]
To shift the pathogenic microbiota to one compatible with periodontal health, the main therapeutic approaches include scaling and root planning (SRP) and surgical intervention. These approaches may not eradicate all pathogenic species due to their invasive potential into gingival epithelial cells and subepithelial connective tissue.[3]
Several antimicrobial agents, delivered by rinsing, irrigation, systemic administration, and local devices, have been used to overcome the limitations of conventional treatment of periodontitis.[25] Systemic antibiotic therapy although successful has various limitations such as the inability to achieve high concentration in gingival crevicular fluid (GCF), adverse drug reactions, the emergence of antibiotic resistance, and uncertain patient compliance. Local drug delivery can provide high drug concentration, minimal side effects, less reliance on patient compliance for taking the medication, and produce concentration profiles which are more constant and last longer than the other delivery systems.[13]
Tetracyclines gain access to bacterial cells by the combined processes of passive diffusion through outer membrane pores and active transfer utilizing an energy-dependent pump in the inner membrane. The rationale for the introduction of doxycycline as an adjunct to periodontal therapy was its broad spectrum bacteriostatic activity that could shift harmful Gram-negative subgingival flora toward Gram-positive flora.[14]
Chlorhexidine is widely known as an effective antiseptic agent used for over 30 years in the management of periodontal disease.[1] Cationic chlorhexidine molecule is rapidly attracted by the negatively charged bacterial cell surface. After adsorption, the integrity of the bacterial cell membrane is altered, which results in a reversible leakage of bacterial low molecular weight components at low dosage (bacteriostatic) or more severe membrane damage at higher dosage (bactericidal).[12]
Another possible approach is the application of hyaluronic acid. It is a nonsulfated glycosaminoglycan and a major component in the extracellular matrix.[9] It is also produced by fibroblasts in the presence of endotoxins. Hyaluronan plays an important anti-inflammatory role through the inhibition of tissue destruction and facilitates healing. It has also been shown to generate bacteriostatic effects.[16]
The purpose of the present study was to compare the efficacy of 0.8% hyaluronic acid gel, 1.5% chlorhexidine gel containing a mixture of chlorhexidine digluconate and dihydrochloride in the ratio of 1:2 (chlosite), and 10% doxycycline hyclate gel as an adjunct to SRP in the management of chronic periodontitis.
| Materials and Methods | | |
Sixteen patients in the age group of 3060 years suffering from chronic periodontitis were selected from the patients visiting the Department of Periodontology, Guru Nanak Dev Dental College and Research Institute, Sunam. Patients with one similar pocket depth (46 mm) at least at the site in all quadrants and with no caries or restorations on selected teeth were included in the study, whereas patients suffering from debilitating diseases, allergic to doxycycline, chlorhexidine, and hyaluronan, smokers, pregnant and lactating women, and alcoholics were not included in the study.
Local drug delivery agents used
- 1.5% Chlorhexidine gel (CHLOSITE GEL)
- 0.8% Hyaluronic acid gel
- 10% Doxycycline gel.
Method
All patients were informed about their participation in the study, and informed consent was taken before the commencement of the procedure. At the first visit, the periodontal examination was carried out and a full mouth supragingival scaling was performed. The baseline visit was after 2 weeks of the screening visit. Periodontal examination was done again, and only those patients with at least one site with pocket depth 46 mm in all four quadrants were selected for the study. Subgingival SRP was carried out, and selected sites were randomly divided into four groups.
- Group I: After SRP, chlorhexidine gel (chlosite) was inserted up to the base of the pocket
- Group II: Doxycycline gel was inserted up to the base of the pocket after SRP
- Group III: After SRP, hyaluronic acid gel was inserted up to the base of the pocket
- Group IV: Only SRP was done.
All the materials were used according to the guidelines recommended by the manufacturer.
The following clinical parameters were recorded:
- Probing pocket depth (PPD)
- Relative attachment level (RAL)
- Gingival index (GI) (Loe and Silness 1963).
Local delivery of drugs
Group I: After the subgingival SRP of the site, the area was dried and isolated with the help of cotton rolls. Chlosite gel was placed into the selected periodontal pocket with the help of a special syringe with a lateral orifice expelling the gel to the base of the periodontal pocket while gradually withdrawing the syringe needle from the base of the pocket.
Group II: After the subgingival SRP of the site, the area was dried and isolated with the help of cotton rolls. Doxycycline gel was administered subgingivally into the selected periodontal pocket with the help of the syringe provided expelling the gel to the base of the periodontal pocket while gradually withdrawing the syringe needle from the base of the pocket.
Group III: The area was dried and isolated with the help of cotton rolls after subgingival SRP. Subgingival administration of hyaluronic acid gel was done into the selected periodontal pocket with the help of the syringe provided with the product expelling the gel to the base of the periodontal pocket while gradually withdrawing the syringe needle from the base of the pocket.
Group IV: Only SRP was done with the help of Gracey curettes.
All the drugs were inserted at the same sitting. The following instructions were then given to the patient:
- To avoid eating hard, crunchy, or sticky foods for 1 week
- To postpone brushing for 12 h
- To avoid touching the treated areas
- Not to use dental floss or any other interdental cleansing aids for a period of 10 days in the treated and the adjacent sites
- Not to use any mouth rinse or any irrigation device.
The patients were recalled after 1 week for evaluation of any inflammatory response and then after 6 weeks and 3 months from the baseline visit to record the clinical parameters.
The data thus obtained were compiled and put into statistical analysis. Ethical approval for this study,(GNDDC/ 2014/V/2415) was provided by ethical committe of GNDDC, Sunam on 15 nov 2014.
| Results | | |
In the present study, at baseline, the mean PPD for Group I was 4.75 ± 0.58 mm which was reduced to 2.69 ± 0.60 mm and 2.25 ± 0.45 mm at 6 weeks and 3 months, respectively [Table 1]. Group I showed a highly significant reduction in PPD from baseline to 6 weeks and baseline to 3 months (P < 0.001) as shown in [Table 2] which was in accordance with the results shown by studies of Kranti K et al. in 2010[29] and Verma A et al. (2012).[29] Significant improvement was seen from 6 weeks to 3 months (P = 0.035). The mean RAL with standard deviation for Group I was 7.94 ± 1.34 mm, 5.81 ± 1.05 mm, and 5.25 ± 0.93 mm at baseline, 6 weeks, and 3 months, respectively [Table 3]. Highly significant improvement was seen for RAL in Group I from baseline to 6 weeks and baseline to 3 months (P < 0.001), as shown in [Table 4]. The mean GI with standard deviation for Group I at baseline was 2.13 ± 0.72 which was reduced to 1.19 ± 0.54 and 0.94 ± 0.77 at 6 weeks and 3 months, respectively [Table 5]. Highly significant improvement was seen in GI from baseline to 6 weeks and baseline to 3 months (P = 0.001). From 6 weeks to 3 months, significant improvement was seen (P = 0.035) [Table 6] which was in accordance with the results shown by studies of Eid HAA et al. (2010)[7] and Reddy KK et al (2013).[25] | Table 1: Mean probing pocket depth and standard deviation for all the groups at different time intervals
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 | Table 2: Intragroup comparison of change in mean probing pocket depth for all groups at different time intervals (Wilcoxon signed-ranks test)
Click here to view |
 | Table 3: Mean relative attachment level and standard deviation for all groups at different time intervals
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 | Table 4: Intragroup comparison of change in mean relative attachment level for all the groups at different time intervals
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 | Table 6: Intragroup comparison of change in mean gingival index for all groups at different time intervals (Wilcoxon signed ranks test)
Click here to view |
For Group II, the mean PPD with standard deviation at baseline, 6 weeks, and 3 months was 4.44 ± 0.73 mm, 3.25 ± 1.00 mm, and 3.00 ± 1.03 mm, respectively, as shown in [Table 1]. Group II showed highly significant improvement in PPD from baseline to 6 weeks and baseline to 3 months (P < 0.001) [Table 2]. Studies by Deo V et al (2011)[15] and Hulami HA et al (2011)[14] have also showed similar results. The mean RAL with standard deviation at baseline was 7.88 ± 1.20 mm, at 6 weeks 7.00 ± 1.63 mm, and at 3 months was 6.31 ± 1.25 mm [Table 3]. Highly significant improvement was seen in RAL from baseline to 6 weeks and baseline to 3 months (P < 0.001) as shown in [Table 4] which was in accordance with the result of a study by Gupta R et al (2008).[13] The mean GI was 2.13 ± 0.72, 1.50 ± 0.52, and 1.25 ± 0.78, respectively, at baseline, 6 weeks, and 3 months [Table 5]. Highly significant improvement was seen for GI from baseline to 6 weeks and baseline to 3 months (P = 0.001) [Table 6] which was in accordance with the studies of Javali MA and Vandana KL (2012).[15]
For Group III, the mean PPD with standard deviation at baseline was 4.38 ± 0.62 mm, 3.19 ± 0.75 mm at 6 weeks, and 2.81 ± 0.66 mm at 3 months [Table 1]. Highly significant improvement in PPD was seen from baseline to 6 weeks and baseline to 3 months (P < 0.001) as shown in [Table 2] which was in accordance with findings of studies by Johannsen A et al (2009)[16] and Eid HAA et al (2010).[7] The mean RAL with standard deviation was 8.31 ± 1.35 mm, 7.06 ± 1.29 mm, and 6.75 ± 1.44 mm at baseline, 6 weeks, and 3 months, respectively [Table 3]. Highly significant improvement in RAL was seen in Group III from baseline to 6 weeks and baseline to 3 months (P < 0.001) [Table 4] which was in accordance with the results of studies by Johannsen A et al (2009)[16] and Eick S et al (2013).[6] The mean GI was 2.38 ± 0.62, 1.75 ± 0.69, and 1.50 ± 0.63 at baseline, 6 weeks, and 3 months, respectively [Table 5]. Highly significant improvement was seen in GI from baseline to 6 weeks and baseline to 3 months. (P = 0.001) as shown in [Table 6] which was in accordance with studies of Gontiya G and Galgali SR (2012).[9]
For Group IV, the mean PPD with standard deviation was 4.19 ± 0.40 mm, 3.13 ± 0.34 mm, and 2.75 ± 0.78 mm at baseline, 6 weeks, and 3 months, respectively [Table 1]. Highly significant improvement in PPD was seen from baseline to 6 weeks and baseline to 3 months (P < 0.001) [Table 6]. The mean RAL was 8.19 ± 1.70 mm, 6.88 ± 1.67 mm, and 6.56 ± 1.37 mm, respectively, at baseline, 6 weeks, and 3 months [Table 3]. Highly significant improvement in RAL was seen in Group IV from baseline to 6 weeks and baseline to 3 months (P < 0.001), as shown in [Table 4]. The mean GI was 2.19 ± 0.75, 1.88 ± 0.62, and 1.56 ± 0.81 at baseline, 6 weeks, and 3 months, respectively [Table 5]. Highly significant improvement was seen in GI from baseline to 6 weeks and baseline to 3 months (P = 0.001) [Table 6]. This reduction is due to the removal of plaque biofilm that leads to a reduction of inflammation and shrinkage of marginal gingival tissues. The inflamed tissue with its inflammatory cell infiltrate and the increased number of capillaries present in the gingival connective tissue is gradually replaced by more collagen-rich tissues. This reduction can also be due to a reduction in the microbial burden in the periodontal pocket or a shift toward less pathogenic microflora.[11]
| Discussion | | |
Bacterial plaque represents the principal etiologic factor involved in the initiation and progression of inflammatory periodontal diseases. Therefore, one of the key elements of periodontal therapy is to achieve a significant reduction or even eradication of suspected periodontal pathogens. Regular and adequate oral hygiene combined with nonsurgical mechanical debridement such as SRP and, in some instances, additional surgical therapy using access flaps have been documented extensively to successfully arrest the progression of periodontal tissue destruction.[8] With the increasing awareness of the bacterial etiology of periodontal diseases and more specifically about the specificity of the microbial involvement, a more direct approach using antibacterial agents has become an integral part of the therapeutic armamentarium. Since the introduction of the controlled release drug delivery concept by Goodson et al. (1985),[10] several local delivery systems, in which the antimicrobial is available at therapeutic levels for several days, have been evaluated in several forms and using different antimicrobials. These include tetracycline fibers, chlorhexidine gel or chip, hyaluronic acid gel, metronidazole gel, and minocycline ointment.
Doxycycline is a broad-spectrum antibiotic of the tetracycline class. It kills bacteria and protozoa by inhibiting protein production like other agents of this class.[31] When delivered systemically, doxycycline has the ability to concentrate in the crevicular fluid (concentration of 14731986 μg/ml at 2 h and gradually decreased to 309 μg/ml at the end of 7 days),[22] and demonstrates a wide spectrum of activity against common periodontal pathogens such as Aggregatibacter actinomycetemcomitans (1985),[30] Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum, Eikenella corrodens, and spirochetes.[18] According to Stoller et al.,[27] doxycycline provided gingival fluid concentrations ranging from over 1900μg/ml at placement to about 300 μg/ml at 7 days.
Al Hulami HA et al. found locally delivered doxycycline to be effective in managing periodontitis as an adjunct to SRP.[14] Javali et al. 2012 demonstrated that 10% doxycycline hyclate gel (Atridox) was as effective as SRP in reducing the clinical signs of periodontitis.[15] According to Tonetti et al., topically administered slow-release doxycycline gel may provide short-term benefits in controlling inflammation and deep pockets after SRP in periodontitis patients.[28]
Hyaluronic acid (HA, hyaluronan) is a linear, widely distributed glycosaminoglycan of the extracellular matrix of mammalian connective tissues, primarily synthesized by mesenchymal cells, and forms the backbone for the organization of proteoglycans establishing links with collagen, fibrin, and different matrix molecules.[19] In a study by Gontiya and Galgali, subgingival placement of 0.2% hyaluronic acid gel along with SRP provided a significant improvement in gingival parameters, but no additional benefit was found in periodontal parameters.[9] However, according to Polepalle et al., subgingival placement of 0.2 ml of 0.8% hyaluronan along with SRP resulted in a significant improvement in both clinical and microbiological parameters.[23]
Chlorhexidine is one of the most effective topical agents, long been used as an effective antimicrobial agent.[4] It is a cationic bisbiguanide with broad antibacterial activity encompassing Gram-positive and Gram-negative bacteria, yeasts, dermatophytes, and some lipophilic viruses. It has also been shown to have inhibitory properties against protease and glycosidic enzymes of various bacteria.[4]
Chlorhexidine has very low systemic toxic activity in humans[26] and does not produce any appreciable resistance to oral microorganisms. Needleman et al. showed that xanthan base chlorhexidine possessed an important property of bioadhesion and showed prolonged adhesion time on the oral mucosa and periodontal pocket.[21] found that subgingival injection of xanthan-based chlosite gel could cause a significantly higher decrease in colony count than that of SRP therapy alone in chronic periodontitis.[1] According to Eid et al., chlosite delivered locally into periodontal diseased sites reduced all subgingival bacteria and no relevant side effects were observed.[7] Chlorhexidine gel has been reported to improve periodontal and microbiological indices when compared to SRP alone and chlorhexidine mouthwash.[24]
Chlosite is based on a gel delivery vehicle which contains a xanthan base which possesses the characteristic of mucoadhesion, which optimizes the retention of the gel vehicle within the periodontal pocket providing a consistent level of the drug in the local environment for an extended period of time.[11] Chlorhexidine gluconate is an active agent against a broad spectrum of microbes. The chlorhexidine molecule, due to its positive charge reacts with the microbial cell surface, destroys the integrity of the cell membrane, penetrates the cell wall, and precipitates the cytoplasm ultimately leading to cell death.[2] Substantivity of chlorhexidine is the result of its affinity for hydroxyapatite, acidic salivary proteins, buccal epithelial cells, and acrylic dentures. It has also been shown to have inhibitory properties against protease and glycosidic enzymes of various bacteria.
Doxycycline is substantive to dentin and cementum, suggesting the potential role for the root acting as a reservoir for subsequent release of the doxycycline.[5] Goodson et al. (1985) in their study concluded that local application of doxycycline resulted in an only transient increase in resistance in oral microflora and no overgrowth of foreign pathogens.[10] The sustained levels achievable with the locally delivered doxycycline provided bactericidal concentrations (i.e., MIC 90 sec) among the vast variety of microorganisms present in the biofilm and may have been able to adequately penetrate the depth of the subgingival biofilm.[4] The properties of doxycycline which seem to be useful in periodontal therapy in addition to its antibacterial pharmacological properties include antiproteolytic and anti-collagenase activity, anti-inflammatory properties to suppress PMN activity inhibition of bone resorption, and the scavenging action on reactive oxygen metabolites. Doxycycline also possesses nonantimicrobial properties that may positively contribute to improved healing. In vitro studies have demonstrated that doxycycline inhibits the conversion of latent proteases into active mature forms and the activation of MMP's by chelating metal ions.[17] The pocket depth reduction could have been enhanced by the possibility of doxycycline adsorbing onto the mineralized dental structures where it may act as a transient reservoir of the antimicrobial agent during a period of substantivity.[20]
When comparisons were made between the groups, the greater reduction in Group I may be due to the fact that chlorhexidine dihydrochloride is a larger and complex molecule that is released over a period of 7 to 8 days at a consistent level that has been shown to be in excess of 20 times the minimum effective dosage to maintain its antimicrobial properties. High initial concentrations of chlorhexidine digluconate give a profound initial disinfectant effect, but concentrations reduce rapidly over a period of about 8 days. Concurrently, the less soluble chlorhexidine dihydrochloride levels rise to achieve a consistently high release of chlorhexidine in the site of placement for at least 2 weeks. This combination might have provided enhanced bactericidal effects during the healing phase which were shown as a slightly improved probing depth as compared to other local drug delivery medicaments.[26]
Hence, the present study showed superior effects of all three drugs when used as an adjunct to SRP. The use of local drug delivery as an adjunct to SRP is better than SRP alone. This study indicates that local drug delivery medicaments are safe and clinical effects achieved with these agents may reduce the need for further advanced and surgical periodontal treatment which would limit morbidity for the subject, the time of treatment, and the cost of therapy.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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