|Year : 2019 | Volume
| Issue : 2 | Page : 35-39
Local drug delivery in the treatment of periodontal diseases
Ashika Sulthana1, RT Arun1, S Krishnaraj1, Rajasekar Sundaram2
1 Department of Periodontics and Implantalogy, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India
2 Department Periodontology, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India
|Date of Submission||31-Dec-2021|
|Date of Decision||05-Jan-2022|
|Date of Acceptance||10-Jan-2022|
|Date of Web Publication||25-Feb-2022|
Department of Periodontics, Rajah Muthiah Dental College and Hospital, Annamalai University, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Periodontitis is a multifactorial, immunomodulatory disease primarily affecting the supporting tissues of the teeth. Various treatment modalities such as mechanical debridement and use of antimicrobial drugs have been used in the treatment of periodontal diseases. Introduction of the local drug delivery (LDD) system is one of the promising approaches in the management of periodontal diseases. It shows better clinical outcomes, when used as an adjunct to scaling and root planning; hence, it cannot be used as a monotherapy. Research efforts have been focused on developing new agents to use in the LDD system.
Keywords: Antimicrobials, local drug delivery, periodontitis
|How to cite this article:|
Sulthana A, Arun R T, Krishnaraj S, Sundaram R. Local drug delivery in the treatment of periodontal diseases. Int J Orofac Biol 2019;3:35-9
|How to cite this URL:|
Sulthana A, Arun R T, Krishnaraj S, Sundaram R. Local drug delivery in the treatment of periodontal diseases. Int J Orofac Biol [serial online] 2019 [cited 2023 Jun 3];3:35-9. Available from: https://www.ijofb.org/text.asp?2019/3/2/35/338385
| Introduction|| |
Periodontitis is defined as a chronic, multifactorial, inflammatory disease affecting the supporting tissues of the teeth, while pathogenic microorganisms play a primary role in the progression of periodontal disease. Periodontal disease starts with the inflammatory reaction involving the gingiva, which when untreated progresses to the supporting tissues of the teeth (i.e., periodontal ligament, cementum, and the alveolar bone) and leads to pocket formation. Various therapeutic approaches have been made to eliminate the pathogenic microorganisms, including mechanical instrumentation or with electronic instrumentation alone or along with the use of chemical therapeutic agents either systemically or locally.
To overcome the certain disadvantages of systemic antimicrobial therapy, the concept of local drug delivery (LDD) was introduced.
| Local Drug Delivery|| |
The concept of LDD was introduced by Dr. Max Goodson in 1979. The main rationale for LDD is to place an antimicrobial or antiseptic agent directly into the periodontal pocket, in contact with the root surface, thus eliminating the pathogenic microorganisms, which is not accessible with hand- or power-driven instruments.
- Based on application (RAMs and slots)
- Personally applied at home by the patient
- Nonsustained (e.g., home oral irrigation)
Professionally applied at dental office
- Nonsustained (e.g., pocket irrigation)
- Sustained (controlled drug delivery devices such as films, strips, chips, fibers, and gels).
Based on duration of drug release
- Sustained release devices
These devices provide drug delivery less than or within 24 h
- Controlled release devices
These devices provide drug release with a minimum of 1 day and a maximum of up to 3 days.
Based on degradation
Based on physical form
- Films (e.g., tetracycline)
- Fibers (e.g., minocycline)
- Chips (e.g., chlorhexidine)
- Injectable forms (e.g., metronidazole, chlorhexidine).
Available forms of local drug delivery
- Strips and compact
- Injectable gels
- Vesicular system
- Microparticle system.
Ideal requirements for a local drug delivery system,
- It should be biodegradable
- It should be effective on pathogenic microflora, not on commensal microflora
- Ease of placement
- The drug delivery system should deliver the drug directly to the base of the pocket
- It should maintain the ideal concentration of the drug for a sufficient duration of time
- It should prevent drug resistance
- It must be retained in place after placement.
- Pockets that are >5 mm, patients with Grade A/B periodontitis
- Patients showing poor compliance with oral hygiene therapy
- Medically compromised patients
- Patients in whom surgical therapy is contraindicated
- Refractory periodontitis
- In conditions such as peri-implantitis
- Grade II furcation involvements.
- When there is an allergy to the particular drug to be used
- Pregnant and lactating patients
- Without scaling and root planing
- In cases of Grade III periodontitis
- As a replacement for surgical periodontal therapy
- As a replacement for systemic antimicrobial therapy
- Patients with a history of infective endocarditis and who have a risk for infective endocarditis.
- A higher concentration of drug (up to 100-fold compared to systemic therapy) is attained at the gingival crevicular fluid (GCF) compared to the systemic antimicrobial therapy
- Drug resistance and superinfection are reduced
- Painless and less invasive procedure
- The technique is suitable for certain agents, which cannot be given through systemic route (e.g., chlorhexidine)
- Drug dosage is less compared to systemic therapy.
- This can be applied only by dental professionals, and it is time-consuming
- Main action of the drug is only on the periodontal pathogens residing in the pocket. Thus, action of drug is not seen on extra pocket sites such as tongue, tonsils, and buccal mucosa
- Technique sensitive, difficult to place in deep periodontal pockets or furcations
- Second appointment is required for nondegradable LDD systems.
Commonly used local drug delivery agents
Tetracyclines are bacteriostatic antimicrobials used as LDD device. It was the first LDD system used by Goodson in 1979. In vitro studies have shown that tetracycline shows excellent substantivity to dentin tooth surfaces. It is available in the form of actisite and Periodontal Plus AB.
Actisite is available in the form of fibers that are 23 cm long and 0.5 cm in diameter, which is nonresorbable, inert, and safe. It is loaded with 25% tetracycline hydrochloride (HCl). The fibers are placed inside the pocket layer by layer and secured with periodontal dressing. It maintains a constant concentration in the GCF for up to 10 days. As it is nonresorbable, it should be removed after 10 days., The resorbable form of tetracycline fibers is commercially available as Periodontal Plus AB; it biodegrades in the pocket within 7 days. Hence, there is no need of second appointment.
Kataria et al. and Panwar et al. applied tetracycline fibers in the periodontal pocket as an adjunct to scaling and root planing, stating that there are significant improvement in clinical parameters and reduction in microbial count in chronic periodontitis.,
It is a bacteriostatic agent commercially available in the form of LDD system as Atridox. It is an FDA-approved 10% gel system comprising 42.5% of doxycycline, and it is composed of 2-syringe delivery system. The subgingival concentration maintains the minimum inhibitory concentration for up to 7 days. Moreover, about 95% biodegrade within 28 days. Garret et al. conducted a randomized clinical trial on patients with chronic periodontitis. The control group received SRP + placebo gel, and the test group received SRP + doxycycline gel. The clinical attachment level was increased in the test group compared to the control group over the mean period of 9 months.
It belongs to the tetracycline group of drugs. It is bacteriostatic in nature, and it has superior substantivity compared to tetracycline. It is available in the form of films, microspheres, and ointment. It is commercially available in the market as Arestin is in the form of microspheres. The 2% gel is encapsulated in the microspheres (20–60 μm). The microspheres gradually release minocycline in the pocket for up to 14 days, and then it resorbs.
Dentomycin is a 2% minocycline HCl gel embedded in a matrix of hydroxyethyl cellulose. Graça et al. conducted a randomized clinical trial using 2% minocycline gel. The trial showed that compared to the SRP group, the SRP + minocycline group shows improvement in clinical parameters.
Chlorhexidine is the second-generation plaque control agent. It plays a primary role in the control of dental plaque and gingivitis. The mechanism of action of chlorhexdine is by reducing pellicle formation, altering bacterial adherence to teeth, and causing cell lysis. It is bacteriostatic at lower concentrations and bactericidal at higher concentrations. Chlorhexidine is available as varnish, gel, and chip to be used as an LDD agent.
It is an orange-brown chip of 4.0 mm × 0.5 mm × 0.25 mm in size consisting of 2.5 mg of chlorhexidine, in a biodegradable matrix of hydrolyzed gelatin, which is approved by the FDA. The chip is placed deep into the periodontal pocket; initially, it releases 45% chlorhexidine in the first 24 h; then, it releases constantly in the linear fashion for the next 7–10 days; hence, it is referred to as biphasic manner.
It is a chip of 4 mm × 5 mm in size with a thickness ranging from 0.25 to 0.32 mm. It consists of 2.5 mg of chlorhexidine derived from 20% chlorhexidine which is embedded in collagen membrane. It degrades within 30 days.
It is a gel system containing 1.5% chlorhexidine of xanthene type. As both chlorhexidine and xanthene are mucoadhesive, it adheres firmly to the pocket, and it easily washes out on GCF or saliva. It degrades within 10–30 days inside the pocket while maintaining a maximum concentration for up to 15 days.
Jeffcoat et al. conducted a study with two groups of SRP and placebo chip and other group received both SRP and chlorhexidine chip as an adjunct. The clinical parameters were improved in SRP + chlorhexidine chip group compared to the SRP + placebo group. In another study by Soskolne, he evaluated the safety and efficacy of SRP alone and SRP + chlorhexidine chip. The mean probing depth reduction was greater in SRP + chlorhexidine group compared to the control group.
It is a bactericidal agent, primarily effective against obligate anaerobes. Its mechanism of action is by disrupting the DNA synthesis. Metronidazole is commercially available in the form of LDD as Elyzol. It is 25% oil-based metronidazole gel. Ainamo et al. compared the effect of subgingival scaling and subgingival scaling with 25% metronidazole in patients with chronic periodontitis. It is found that the probing pocket depth and bleeding on probing are reduced in metronidazole group. Noyan et al. compared the effects of scaling and root planing, systemic metronidazole, and scaling and root planing along with local administration of 25% metronidazole gel. The results of the study have shown that the scaling and root planing along with local administration of metronidazole gel has shown better clinical and microbiological parameters compared to the other groups.
It is used as LDD system in the form of 0.5% gel. Agarwal et al. evaluated the efficacy of subgingivally delivered 0.5% clarithromycin gel as an adjunct to scaling and root planing in chronic periodontitis smoking subjects, and it shows significant result in improving clinical parameters.
| Drugs for Osseous Defects|| |
It belongs to the bisphosphonate group of drugs. The mechanism of action is by inhibiting the action of osteoclasts, thus reducing bone resorption. As systemic administration of bisphosphonate causes gastrointestinal disturbances, to minimize the adverse effects, it is limited to local delivery and it can attain higher concentration in the GCF compared to the systemic route.
Rocha et al. in their study evaluated the effect of 1% alendronate gel as a LDD agent as an adjunct to scaling and root planing in type 2 diabetes mellitus patients with chronic periodontitis. It is found to be effective in reducing bleeding on probing, improving clinical attachment level, and increasing bone fill when compared to placebo gel.
Simvastatin is a potent inhibitor of HMG–CoA reductase enzyme, which is a key enzyme in cholesterol synthesis. It stimulates bone formation by increasing the expression of bone morphogenic protein-2 and endothelial growth factor. Pradeep et al. in their study evaluated the bone fill by radiographic assessment by using computer-aided software and found significant bone fill in sites treated with simvastatin along with LDD.
| Newer Trends|| |
Local delivery of growth factors
Growth factors such as platelet-derived growth factor, vascular endothelial growth factor, fibroblast growth factor, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen are introduced in LDD. They effectively involved in mitogenesis, angiogenesis, bone turnover, and wound regeneration.,
Colloidal drug carriers
It includes vesicles, liposomes, nanoparticles, emulsions, and micelles which are largely used as LDD agents because of their ease of placement. Colloidal drug carriers increase the bioavailability of the drug in the pocket and increase their specificity of action toward the tissue.
Herbal agents individually or with a combination of several herbal agents are also used as an LDD.
| Conclusion|| |
Advancement in the medical field leads to newer therapeutic agents and different modes of controlled drug delivery systems. One of the problems faced is to attain a sufficient concentration of drug at the target site. Hence, LDD system was introduced as it attains sufficient concentration of target site, and it has certain advantages over systemic mode of admissions such as less dosage, less side effects, and drug resistance. Thus, LDD is used as adjunct to scaling and root planing in treating periodontal diseases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sudhakar DU, Gethsie KR, Priyanka H, Zinneerah SF. Local drug delivery drugs and systems. Int J Appl Dent Sci 2020;6:70-3.
Rajeshwari HR, Dhamecha D, Jagwani S, Rao M, Jadhav K, Shaikh S, et al.
Local drug delivery systems in the management of periodontitis: A scientific review. J Control Release 2019;307:393-409.
Pattanshetti JI, Tiwari I, Singh G, Tazyeen F, Parihar AS, Khare N. Local drug delivery modalities in treatment of periodontitis: A review. J Int Oral Health 2016;8:296-301. [Full text]
Mundinamane D, Suchetha A, Venkataraghavan K, Garg A. Newer trends in local drug delivery for periodontal problems – A preview. Int J Contemp Dent 2011.
Ramesh A, Prakash AP, Thomas B. Local drug delivery in periodontal diseases. A review. J Health Allied Sci NU 2016;06:074-9.
Greenstein G. Local drug delivery in the treatment of periodontal diseases: Assessing the clinical significance of the results. J Periodontol 2006;77:565-78.
Kaur S. Local drug delivery in the treatment of periodontitis. Indian J Compr Dent Care 2016;2:Issue 2.
Kornman KS. Controlled-release local delivery antimicrobials in periodontics: Prospects for the future. J Periodontol 1993;64:782-91.
Rajesh KS, Arun Kumar MS, Reshmi TS, Pooja M, Hedge S, Boloor V. An overview on new classification of periodontal and peri- implant diseases and conditions 2017. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) 2020;19:52-5.
Soskolne WA. Subgingival delivery of therapeutic agents in the treatment of periodontal diseases. Crit Rev Oral Biol Med 1997;8:164-74.
Offenbacher GS. Periodontal disease treatment by local drug delivery. J Clin Periodontol 1984;56:265-72.
Trombelli L, Tatakis DN. Periodontal diseases: Current and future indications for local antimicrobial therapy. Oral Dis 2003;9 Suppl 1:11-5.
Goodson JM. Antimicrobial strategies for treatment of periodontal diseases. Periodontol 2000 1994;5:142-68.
Venkatasubramanyam A, Chakravarty D. Local drug delivery in periodontics – A review. Int J Med Biomed Stud 2018;05:25-7.
Baker PJ, Evans RT, Coburn RA, Genco RJ. Tetracycline and its derivatives strongly bind to and are released from the tooth surface in active form. J Periodontol 1983;54:580-5.
Ashtaputre V, Limaye M. Local drug delivery in periodontics: A tactical entreaty. Journal of Research in Pharmaceutical Science 2014;2:6-11.
Litch JM, Encarnacion M, Chen S, Leonard J, Burkoth TL. Use of the polymeric matrix as internal standard for quantitation of in vivo
delivery of tetracycline HCI from Actisite® tetracycline fiber during periodontal treatment. J Periodontal Res 1996;31:540-4.
Kataria S, Chandrashekar KT, Mishra R, Tripathi V, Galav A. Effect of tetracycline HCL (periodontal plus AB) on Aggregatibacter actinomycetemcomitan
s levels in chronic periodontitis, Oral biology and dentistry; ISSN 2053-5775;3:Article 2.
Panwar M, Gupta SH. Local drug delivery with tetracycline fiber: An alternative to surgical periodontal therapy. Med J Armed Forces India 2009;65:244-6.
Steven garrett, Lonnie jhonson, Drisko, Donald.F.Adam, Carl et al. Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. Journal Periodontol 1999;70:490-503.
Müller HP, Lange DE, Müller RF. Failure of adjunctive minocycline-HCl to eliminate oral Actinobacillus actinomycetemcomitans
. J Clin Periodontol 1993;20:498-504.
Pragati S, Ashok S, Kuldeep S. Recent advances in periodontal drug deleivery systems. Int J Drug Deliv 2009;1:1-14.
Graça MA, Watts TL, Wilson RF, Palmer RM. A randomized controlled trial of a 2% minocycline gel as an adjunct to non-surgical periodontal treatment, using a design with multiple matching criteria. J Clin Periodontol 1997;24:249-53.
M K Jeffcoat 1, K S Bray, S G Ciancio, A R Dentino, D H Fine, J M Gordon, J C Gunsolley, W J Killoy et al. Adjunctive use of a subgingival controlled-release chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planing alone; J Periodontol 1998;69:989-97.
Greenstein G, Polson A. The role of local drug delivery in the management of periodontal diseases: A comprehensive review. J Periodontol 1998;69:507-20.
Ainamo J, Lie T, Ellingsen BH, Hansen BF, Johansson LA, Karring T, et al.
Clinical responses to subgingival application of a metronidazole 25% gel compared to the effect of subgingival scaling in adult periodontitis. J Clin Periodontol 1992;19:723-9.
Noyan U, Yilmaz S, Kuru B, Kadir T, Acar O, Büget E. A clinical and microbiological evaluation of systemic and local metronidazole delivery in adult periodontitis patients. J Clin Periodontol 1997;24:158-65.
Esha Agarwal 1, A R Pradeep, Pavan Bajaj, Savitha B Naik. Efficacy of local drug delivery of 0.5% clarithromycin gel as an adjunct to non-surgical periodontal therapy in the treatment of current smokers with chronic periodontitis: a randomized controlled clinical trial: J Periodontol 2012;83:1155-63.
Binderman I, Adut M, Yaffe A. Effectiveness of local delivery of alendronate in reducing alveolar bone loss following periodontal surgery in rats. J Periodontol 2000;71:1236-40.
Rocha M, Nava LE, Vázquez de la Torre C, Sánchez-Márin F, Garay-Sevilla ME, Malacara JM. Clinical and radiological improvement of periodontal disease in patients with type 2 diabetes mellitus treated with alendronate: A randomized, placebo-controlled trial. J Periodontol 2001;72:204-9.
Morris MS, Lee Y, Lavin MT, Giannini PJ, Schmid MJ, Marx DB, et al.
Injectable simvastatin in periodontal defects and alveolar ridges: Pilot studies. J Periodontol 2008;79:1465-73.
Pradeep AR, Thorat MS. Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: A randomized clinical trial. J Periodontol 2010;81:214-22.
Jason W Cooke 1, David P Sarment, Louis A Whitesman, Sarah E Miller, Qiming Jin, Samuel E Lynch, et al. Effect of rhPDGF-BB delivery on mediators of periodontal wound repair; Tissue Eng 2006 Jun;12:1441-50.
Pinheiro ML, Feres-Filho EJ, Graves DT, Takiya CM, Elsas MI, Elsas PP, et al.
Quantification and localization of platelet-derived growth factor in gingiva of periodontitis patients. J Periodontol 2003;74:323-8.