Comparative Clinical Evaluation of Two Local Drug Delivery Agents (Neem Chip and Turmeric Chip) in Chronic Periodontitis: An Experimental Study

INTRODUCTION

Chronic periodontitis is an inflammatory condition of the supporting tissues of the teeth caused primarily by mixed microbial infection.¹ This complex inflammatory process results in loss of periodontal tissue attachment and alveolar bone resulting in periodontal pocket formation. The ultimate goal of all periodontal therapy is to restore the health of inflamed tissue, eliminate the diseased pockets, and reduce the number of pathogenic microorganisms.² Thus, surgical and nonsurgical treatment modalities for removing plaque biofilm are essential for the management of chronic periodontitis.³

Scaling and root planing (SRP) procedures have been used as the “gold standard” for nonsurgical mechanical therapy.⁴ This conventional therapeutic module effectively decreases the microbial load, but recolonization of the same cannot be prevented.⁵ Systemic antibiotics are often used as an adjuvant to this treatment. To avoid the undesired effect of systemic antibiotics, Goodson gives the concept of controlled drug delivery for treatment of chronic periodontitis and observed that 100-fold higher concentrations of the drug can be attained through the local route as compared to systemic drug regimen without side effects. This helps to avoid the development of drug resistance at nonoral body sites.^6,7

Various antimicrobial agents such as tetracycline, 10% doxycycline, 2% minocycline, metronidazole, and chlorhexidine (CHX) gluconate have been used and investigated as local drug delivery (LDD) in the treatment of periodontal diseases.⁸ In today’s era, research is being focused mainly on the use of natural products as LDD agents. There have been various formulations under study which increased our curiosity about the medicinal value of natural products such as turmeric, aloe vera, neem, tulsi, cocoa husk, and pomegranate, and these all are tested widely these days.⁹

Neem and turmeric have a unique anti-inflammatory property. The advantage that these herbal plants can be fabricated into chips and delivered at the local site goes a long way in the management of the local inflammatory process. Easy application of these chips and no side effects of herbal products leads to our thinking of utilizing them in chronic periodontitis treatment. Hence, in this study, we intend to evaluate the efficacy of these herbal chips as LDD agents adjuvant to SRP vs SRP alone in the treatment of chronic periodontitis.

MATERIALS AND METHODS

RESULTS

Mean PI at 1 month for group I, II, and III was 1.33 ± 0.28, 1.37 ± 0.28, and 1.66 ± 0.27, respectively. Improvement in mean PI of group I and group II is significant when compared with group III (p < 0.05). At 3 months, the mean PI was 1.29 ± 0.29, 1.37 ± 0.29, and 1.44 ± 0.30 for group I, II, and III, respectively. Improvement in mean PI from 1 to 3 months is not significant in any group (p %3E; 0.05). This PI score for three test groups at baseline, 1 month, and 3 months is shown in Table 1.

Intergroup comparison showed no significant difference in GI at baseline. Mean GI at 1 month for group I, II, and III was 1.20 ± 0.31, 1.24 ± 0.26, and 1.31 ± 0.39, respectively. Improvement in GI is significant in all groups at one month (p < 0.05). At 3 months, mean GI was 1.29 ± 0.28, 1.37 ± 0.29, and 1.39 ± 0.35 for group I, II, and III, respectively. Improvement in mean GI of both group I and group II at 1 month is significant when compared with group III (p < 0.05). This GI score for three test groups at baseline, 1 month, and 3 months is shown in Table 2

Probing pocket depth at 1 month for group I, II, and III was 4.16 ± 0.88, 4.21 ± 0.61, and 4.63 ± 0.68, respectively (p %3C; 0.05 for all groups). At 3 months for group I, II, and III was 3.91 ± 0.85, 4.18 ± 0.69, and 4.32 ± 0.62, respectively. Improvement in mean PPD of group I and group II is significant when compared with group III (p < 0.05). However, improvement in mean PPD of group I and II in comparison to group III is not statistically significant at 3-month follow-up (p %3E; 0.05) as shown in Table 3.

Relative attachment level at 1 month for group I, II, and III was 8.41 ± 1.59, 8.43 ± 1.66, and 9.01 ± 1.50, respectively. At 3 months for group I, II, and III was 8.26 ± 0.27, 8.37 ± 0.3, and 8.74 ± 0.29, respectively. Improvement in mean RAL of group I and group II is significant when compared with group III (p < 0.05) at 1 month. However, improvement in mean RAL of both test groups in comparison to group III is statistically insignificant at 3-month follow-up (p > 0.05) as shown in Table 4.

DISCUSSION

Since the prime etiological factor is plaque formation, so till date the goal of periodontal therapy is aimed at removing supra- and subgingival plaque biofilm by mechanical debridement, keeping this context in mind study is planned to compare control group SRP along with placebo chip (Hawthorne effect) to herbal LDD agents adjunct to SRP.

Local drug delivery agents directly act on periopathogens residing in periodontal pockets and aids in controlling the disease. They are available as a gel, strips, nanosphere, microspheres, chips, etc. The various locally delivered antimicrobials agents available are listed below:

• Tetracycline fibers.
• Metronidazole gel.
• Minocycline ointment.
• Chlorhexidine chips.
• Doxycycline hyclate in a resorbable polymer.
• Resorbable tetracycline in fibrillar collagen.
• Minocycline microspheres.
• Azithromycin gel, etc.¹²

Oral rinses and irrigating devices are easy to use and commonly employed but irrigation system is not much successful in managing periodontitis as the desired concentration of a drug is not achieved in the pocket, as well as there is inadequate penetration of drug in the deep pocket.¹³

In the present study, we have used antimicrobial agents in form of biodegradable chips as this route provides more sustainability for the drug. One of the commercially available FDA-approved LDD agents containing 0.02% chlorhexidine (Periochip) is considered as the gold standard by some authors in the treatment of periodontitis.^14,15 The disadvantage is that they are expensive, so we used indigenously produced biodegradable chips that were cost-effective.

We have used neem (Azadirachta indica) and turmeric (Curcumin longa) in the treatment of periodontitis because of their anti-inflammatory, antimicrobial, antioxidant, immunostimulant, and anticancer properties. Turmeric is an easily available, renewable resource, and cost-effective, so used in various inflammatory diseases including chronic periodontitis as a LDD agent.¹⁶ Curcumin acts as an anti-inflammatory agent by down-regulating the activity of cyclooxygenase-2 (COX-2), lipoxygenase, and inducible nitric oxide synthase (iNOS) enzymes.¹⁷

Neem twigs are in use since ancient times for cleaning teeth and gum massage. The antibacterial activity of neem against periodontal pathogens has been proven in various studies. Rao et al. have proved the efficacy of neem in reducing plaque cultures and gram-negative bacteria as compared to the other denitrifies which are available commercially.¹⁸ Studies done by Chaterjee et al. and Chaudhary et al. showed that mouth rinse prepared from leaf extract is highly efficacious in controlling gingivitis.^19,20

It is seen that the effect of the locally delivered controlled-release drug is evident up to 11 weeks after administration. Hence, planned our follow-up at 1-month and 3-month interval.²¹

In the present study, we have used Neem and Turmeric because these two products are well known among our study population and also easily acceptable. Moreover, both Neem and turmeric chips were available commercially, cost-effective, and can be stored at room temperature. On comparison of neem chip and turmeric chip as an adjunct to SRP vs SRP alone in microbial plaque accumulation (PI) from baseline to 1 month and 3 months by using Silness and Loe, PI we found that after 1-month follow-up group I and II with neem and turmeric were more efficient than group III in reducing plaque. Results can be attributed due to the additional antibacterial properties of these LDD agents. Contrary to the results of our study, Singh et al. stated that no significant difference in PI from baseline to 1 month was seen while comparing curcumin chip as an adjunct to scaling and root planing.²² Similar to our results, study done by Vennila et al. in 2016 showed that plaque accumulation decreases significantly on day 7 and 21.¹³ At 3 months, no difference in plaque accumulation among the test and control group.

In our study, changes in GI showed a significant reduction at 1 month. At 3 months, there is a slight increase in gingival scores that can be attributed due to noncompliance to oral hygiene instructions. Comparison of PI and GI of all three groups represented in Figure 2. Gottumukkala et al. showed that curcumin gel and chlorhexidine were better in reducing the gingival inflammation at 1 month but at 3 months chlorhexidine group was better as there was a recurrence of inflammation in the curcumin group. Contrary to our results, Singh et al. showed after a 1-month interval GI have no significant difference in all three groups Periochip + SRP, curcumin chip + SRP, and SRP.^23,24

Both the test groups showed a decrease in PPD and RAL from baseline to 1 month significantly as compared to the control group. Jain et al. in a similar study compared the neem chip + SRP with SRP alone and the results were in favor of our study at 6 weeks.²⁴ Contrary to our results, Mehta et al. in 2015 used neem extract as an LDD agent and found it to be marginally better than SRP but not significant.²⁵ Comparison of PPD and RAL at baseline 1 month and 3 months is shown in Figure 3.

Both agents neem and turmeric chip were found to be effective in reducing clinical parameters such as PI, GI, PPD, and RAL.

CONCLUSION

Neem and turmeric as LDD agents adjunct to SRP are more effective in controlling chronic periodontitis as compared to SRP alone in a short duration of 1 month. However, the long-term effects of these agents are still debatable. Further studies with large sample size, long-term follow-ups, and microbiological culturing for evaluating the specific bacterial inhibitory effects of indigenously produced herbal chips are required.

CLINICAL SIGNIFICANCE

These herbal substitutes, i.e., neem chip and turmeric chip are natural products free from side effects and cost-effective LDD agent in managing chronic periodontitis.

ACKNOWLEDGMENTS

We would like to thank Dr Sreenivasan, Principal Guru Nanak Institute of Pharmacy, Ibrahimpatnam, Hyderabad, for helping in herbal chip fabrication.

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