TITLE

EVALUATION OF CLINICAL EFFICACY OF LOCALLY DELIVERED NOVEL COMPOSITE GEL  CONTAINING BROMELAIN  AS AN ADJUNCT TO NONSURGICAL PERIODONTAL THERAPY. 

INTRODUCTION

Periodontal disease [PD] is an immuno-inflammatory destructive disease of periodontal tissues characterized by the loss of soft tissue attachment and alveolar bone loss caused by pathogenic microorganisms resulting in pocket formation and/or gingival recession [1]. Periodontal disease is one of the most common chronic infectious diseases among adults and is caused by the accumulation of bacterial biofilm. [1,2]

The periodontal pocket is a pathologically deepened gingival sulcus caused by the apical migration of junctional epithelium. The coronal movement of the gingival margin without the destruction of underlying periodontal tissues creates a pseudo pocket or gingival pocket, whereas the apical migration of the junctional epithelium with the destruction of supporting periodontal tissues is responsible for developing a true pocket or periodontal pocket. [3]

Non-surgical periodontal therapy (NSPT) is considered as a “golden standard” treatment protocol for periodontal pockets because it involves scaling and root planing (SRP) to remove supra and subgingival biofilm, plaque and calculus from diseased root surfaces. [4,5] It is proven that the non-surgical approach is an effective treatment strategy with periodontal pockets measuring less than the critical probing depth of 4.2 mm. However, in cases of deep periodontal pockets, surgical periodontal therapy along with periodontal regeneration stands to be a viable option, as complete debridement of biofilm and local deposits remains crucial due to the presence of extensive periodontal tissue destruction.

Periodontal pockets present an ideal site for treatment using localized drug delivery systems. Within the field of periodontics, there are established approaches for delivering drugs directly in to subgingival sites or periodontal pockets. These systems release antimicrobial agents either instantly or in a controlled and sustained manner, effectively countering microbial threats while minimizing potential adverse effects on non-oral parts of the body. Currently, a range of local drug delivery systems are available, including fibers, gels, strips, films, irrigating systems, and microparticles. [6 7 8].

BROMELAIN is best known for its anti-inflammatory, analgesic and anti plaque effect in the oral cavity. Bromelain has also been reported to have profound effect on immunity and gingivitis.[9]. Bromelain is proteolytic enzyme containing one sulfhydryl group. It is found in juice and stem of pineapple and is prepared through ultrafiltration, centrifugation and lypophilizin[10]. Bromelain show an anti-inflammatory response by reducing prostaglandin E2[PGE2]and cyclooxygenase 2 (co-x2) synthesis [11]. It also inhibits bacterial enterotoxin production [12]. It can be used as an  analgesic after tooth extraction and  increases absorption of antibiotics like Amoxicillin and tetracycline.[13,14]

In rural/remote areas where there are lack of resources and in medically compromised individuals or physically or mentally challenged children where periodontal surgical therapy is perplexing to be performed, there is a need for simultaneous hard and soft tissue regeneration at the very first visit/ appointment of the patient undergoing SRP. There is a need to introduce a novel prodigious material that would not only help in the soft and hard tissue regeneration of the periodontal tissues but also serve to reduce the inflammatory load at the infected site selectively.  Nevertheless, no literature till date is available evaluating the effect of local delivery of novel composite gel containing Bromelain as an adjunct to SRP in patients with periodontitis. So, this study aims to evaluate clinical efficacy of locally delivered novel composite gel containing Bromelain as an adjunct to nonsurgical periodontal therapy.

Aims and Objectives

1. Evaluation of the clinical efficacy of locally delivered novel composite gel containing Bromelain  as an adjunct to nonsurgical periodontal therapy in the treatment of periodontitis.
2. To determine the effect of novel composite gel containing Bromelain on reduction in gingival inflammation.
3. To determine the effect of novel composite gel containing Bromelain on reduction in pocket depth and gain in clinical attachment level.

Review of literature                                   

 1. In a 2014 study, NC Praveen et al.[16] conducted an in vitro evaluation of the antibacterial efficacy of bromelain against common periodontal pathogens. The experiment assessed the Minimum Inhibitory Concentration (MIC) of bromelain on isolated strains of Streptococcus mutans, Enterococcus faecalis, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis. The findings revealed that S. mutans exhibited the highest sensitivity to bromelain at the lowest concentration. In comparison, E. faecalis and P. gingivalis also demonstrated sensitivity at lower concentrations, whereas A. actinomycetemcomitans required a higher concentration to achieve similar effects.

2.  In a 2018 study, Ali Zarandi Masoumeh Faramerzi et al. [17] investigated the effects of bromelain on periodontal indices in the non-surgical treatment of patients with chronic periodontitis. This double-blind clinical trial involved 80 patients with chronic periodontitis and otherwise healthy systemic status, divided into two groups of 40 each. One group received a 500 mg bromelain capsule twice daily, one hour before meals, while the other group was given a placebo. After eight weeks of treatment, the results showed a significant reduction in periodontal indices, including the gingival index, probing depth, and plaque index, in the bromelain group compared to the placebo group.

3.   In 2023, Puja C. Yavagal et al. [18]  studied the antimicrobial efficacy of 4.8% bromelain extract as an irrigation solution against Porphyromonas gingivalis in periodontal pockets. The results showed a significant reduction in P. gingivalis counts post-irrigation.               

4. In another 2023 study, Houssein Babazade et al. [19] conducted a double-blind, randomized, placebo-controlled clinical trial to evaluate bromelain’s impact during periodontal surgery. Twenty-eight patients undergoing pocket elimination surgery were divided into two groups: one received 500 mg of bromelain one hour before meals, and the other received a placebo. After four weeks, the bromelain group showed reduced bleeding on probing and a lower plaque index, though there was no significant change in the gingival index compared to the placebo group.

Primary Research Question: What is the effect of locally delivered bromelain containing novel composite gel when delivered as an adjunct to SRP in the treatment of periodontitis?

Null Hypothesis: There is no additional beneficial effect of locally delivered bromelain containing novel composite gel when delivered as an adjunct to SRP in the treatment of periodontitis.

Alternative Hypothesis: There is considerable beneficial effect of locally delivered bromelain containing novel composite gel along with SRP in the treatment of periodontitis.

Materials and Methods

The present study is a prospective, double-blind, split mouth, randomized clinical trial.

Study Area: The study will be conducted among patients visiting the outpatient Department of Periodontics and Implant Dentistry, Ranjeet Deshmukh Dental College and Research Centre, Nagpur.

Sample size:

The sample size was determined based on the results of a study by Kepu V Raghava et al.[20] 2019. As per previous study the effect size obtained by using the mean probing pocket depth(PPD) for the patient group was 0.47. However, in the present study a more stringent effect size of 0.8 was adopted which resulted in sample size of  84  ( 42 per group) ,which provided the desired effect with 95% confidence 80% power.Calculated by

Inclusion criteria

1. Systemically healthy patients within the age group of 18–65 years.

2. Patients should have at least 14 natural teeth in the oral cavity.

3. Patients with no history of allergies.

4. Patients who are diagnosed with generalized periodontitis of stages II and III (According to World Workshop of Periodontology, 2017 with bilateral periodontal pockets with probing pocket depth of between 4 and 6 mm.

 Exclusion Criteria

1. Smokers.

2. Pregnant and lactating mothers.

3. Patients who received radiotherapy, chemotherapy or immunosuppressive treatment, systemic corticosteroids, and/or anticoagulants 30 days prior to intervention.

4. Patients with any systemic disease.

5. Patients under the influence of non-steroidal anti-inflammatory drugs (NSAIDS) or any other anti-inflammatory medications, antibiotics, steroids that can alter the course of periodontitis progression and treatment.

The selected patients will be taken for SRP procedure. The bilateral pockets will be randomly divided into the following treatment groups.

Group 1: Sites treated with SRP followed by local delivery of placebo gel (n=42)

Group 2: Sites treated with SRP followed by novel composite gel containing Bromelain (n=42))

On their first visit, all patients will be clinically examined and the following indices will be recorded using UNC 15 Periodontal Probe-Plaque index (PI) (site specific Plaque index by Löe and Silness in 1967), Gingival index (GI) (Löe and Silness, 1963), Sulcus bleeding index (SBI) (Muhlemann and Son, 1971), Probing pocket depth (PPD), and Clinical attachment level (CAL).

These indices or outcomes will be measured at all six surfaces of the selected tooth (mesio-buccal, mid-buccal, disto-buccal, mesio-lingual, mid-lingual, and disto-lingual). The gingival parameters including the colour, contour, consistency, surface texture, position and width of keratinized tissue will also be recorded. These parameters will be recorded at baseline and 3 and 6 months after the therapy.

Randomization and Blinding

The randomization will be carried out using computer generated table of random numbers. The allocated groups will be concealed using opaque sealed envelopes, which will be opened prior to the sub-gingival delivery of novel composite gel containing Bromelain. The study will be double-blind, where both the participants and investigator will be unaware of the substance to be delivered.

Technique for Local Delivery of novel composite gel containing Bromelin

After baseline examination the test sites will be treated with SRP followed by subgingival administration of novel composite gel containing Bromelain through blunt cannula, and control sites will be treated with SRP followed by subgingival administration of saline as a placebo through a blunt cannula.

Method of data analysis

Statistical analysis will be performed using Statistical Package for Social science (SPSS) version 20 for Windows. Descriptive quantitative data will be expressed in mean and standard deviation respectively. Data normality will be checked by using Shapiro – Wilk test. Comparison between two groups will be done using parametric t test and comparison between more than two groups will be done using ANOVA test (if the data follows normality conditions) or non-parametric Mann Whitney U test (if data does not follow normality conditions).  Association between categorical variables will be checked using chi square test (non-parametric test).