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Research

Authors : Dr. Erwin Faller,Dr. Srinivas Sulugodu Ramachandra,Dr. Fawzia Abdullah.

Abstract:

Introduction:Chronic periodontal disease is defined as an inflammatory disease of the supporting tissues of teeth caused by microorganisms in the dental biofilm, resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket formation and gingival recession.Anti-microbial agents have been used both systemically and locally as adjuncts to mechanical treatment.Local administration of the agent/drug decreases the chances of development of drug resistance, increases the total concentration of the drug at the diseased site and reduces the possibility of occurrence of systemic side effects. This article discusses the methodology involved in preparation of a vehicle to carry active drug molecules to the periodontally diseased site.

Material and Methods:Chitosan powder and acetic acid was used to make the chitosan based periodontal chip. This mixture of acetic acid and chitosan was dissolved in water and sonicated to form a homogenous combination. A stainless steel mould was prepared through which the chitosan based chip of desired dimensions can be produced. The slot in the stainless steel mould was prepared to produce a chip of desired dimensions.

Results and Discussion:The prepared chitosan base can be used as a vehicle to carry various active ingredients to the periodontal diseased site. Spectrophotometry can be used to confirm the presence of the active ingredient in the chitosan base. The interaction of chitosan with active ingredient is also revealed by spectrophotometry.Curcumin, various antibiotic agents like metronidazole, anti-allergic agents can be mixed at optimal concentrations to be integrated into the vehicle.

Introduction:

Periodontal disease and dental caries compromise the two most important reasons for tooth loss in all populations. Chronic periodontal disease is defined as an inflammatory disease of the supporting tissues of teeth caused by microorganisms in the dental biofilm, resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket formation and gingival recession.1 Periodontal diseases are treated primarilyby mechanical therapy involving scaling, root planing and periodontal surgeries. Treatment aims at arresting the inflammation and stopping the loss of attachment by removal and control of the supra- and sub-gingival biofilm and establishing a local environment and microflora compatible with periodontal health.1Various anti-microbial agents have been used as adjuncts to periodontal therapy with some amount of success.Periodontal bacteria are not planktonic bacteria and instead remain in a biofilm environment.2 The fluid filled channels in the biofilm environment provides an ideal niche for growth of aerobic bacteria initially and for growth of anaerobic bacteria in further advanced stages. The biofilm environment alsohinders the penetration of antibiotics thus safe guarding the bacteria within the biofilm.2,3

Disruption of the biofilm is essential for antimicrobial activity. Mechanical therapy serves to disrupt the biofilm environment.3Due to these reasons, non-surgical periodontal treatment remains the corner stone of periodontal therapy. Anti-microbial agents have been used both systemically and locally.4Systemically administered antimicrobial agents have many disadvantages like minimal concentration of the drug reaching the diseased site, and numerous systemic side effects like nausea, vomiting and gastro-intestinal upset. Systemic antimicrobial agents cannot be prescribed for a long period of time due to the problem of drug resistance. To, overcome the above mentioned disadvantages, drugs were delivered locally to the diseased site.4,5

Local administration of the agent/drug decreases the chances of development of drug resistance, increases the total concentration of the drug at the diseased site and reduces the possibility of occurrence of systemic side effects.4,5Local drug delivery agents are classified based on its ability to resorb/biodegrade on its own into:Biodegradable and Non-biodegradable.Biodegradable local drug delivery agents resorb on their own within a period of 7 to 10 days. So, patients do not need another appointment for removal of the agent. Non-biodegradable agents does not resorb in the periodontal pockets. So, the patient has to be scheduled for another appointment for removal of the chip. Local drug delivery agents which are biodegradable have an added advantage over the non-biodegradable ones.4,5Biodegradable agents reduce the overall treatment time for both the patient and the clinician.

Chitosan is available in the form of powder and is produced by deacetylation of chitin, which is the structural element in the exoskeleton of crustaceans (such as crab,shrimps and lobster) and cell wall of fungi.6Chitosan being biodegradable has a natural advantage over other vehicles.This article discusses methodology involved in preparation of a vehicle to carry active drug molecules to the periodontally diseased site. Through the use of vehicle various active drug molecules can be carried to the diseased site without systemic side effects.

Material and Methods

Chitosan powder and acetic acid was used to make the chitosan based periodontal chip. All procedures and materials were done under aseptic conditions. One percent of acetic acid was added to 5 gm of chitosan powder and mixed thoroughly. This mixture of acetic acid and chitosan was dissolved in water and sonicated to form a homogenous combination. The dissolving of water was done at 50 ml, 100 ml, 150 ml and 200 ml. The mixture of chitosan powder and acetic acid is incubated overnight (Figure 1). The mixture was poured into rectangular designed glass molds lined with aluminium foil (Figure 2). A stainless steel mould was prepared which could prepare the chitosan based chip of desired dimensions (Figure 3). The slot in the stainless steel mould was prepared to produce a chip of desired dimensions (Figure 4). Thickness, length and breadth of the chip was calculated based on the dimensions of the standard chips used in the treatment of periodontal diseases. The slot has two ends: the flat end and the curved end. The curved end produces the curve in the chip which eventually goes towards the bottom of the pocket. Dimensions of the chip was 10 mm length, 2 mm width and 0.5 mm in thickness. The mixture of chitosan and acetic acid was added in the stainless steel mould and a chip of the above mentioned dimensions was prepared (Figure 4).

   
Fig 1: Image of chitosan powder mixed with acetic acid at various dilutions of 50ml,100ml,150ml and 200ml.  Fig : 2 Image of the mixture of and acetic acid being incubated overnight and poured into glass milds. 
   
Fig 3: Image of the stainless steel and mould used to make the chitosan based chip of desired dimensions.  Fig : 4 Image of the stainless steel mould used to make the chitosan based chip.The yellow arrow indicate the slot prepared in the mould of desired dimensions.The chip produced will correspond to the dimensions of the slot.The inset at the bottom of the image shows the chitosan based chip of desired dimensions. 

Discussion: 

Chitosan is non-toxic, biocompatible and biodegradable. Chitosan is also mucoadhesive, and releases of drugs/active molecules over a period of time. These properties make chitosan an ideal material to be used as novel drug delivery systems. The prepared chitosan base can be used as vehicle to carry various active ingredients/molecules. Curcumin, green tea catechins various anti-microbial agents like metronidazole, anti-allergic agents can be mixed at optimal concentrations to be integrated into the vehicle. The solvent system used in our case was acetic acid. Ascorbic acid can also used as solvent to dissolve the chitosan powder. Spectrophotometry should be used to confirm the presence of the active ingredient in the chitosan base. The amount of the active molecule/ingredient and the percentage of the active molecule in the chitosan can be determined by spectrophotometry. The interaction of chitosan with active ingredient is also revealed by spectroscopy.Spectrophotometry is the quantitative measurement of the reflection or transmission properties of a material as a function of wavelength. The colorimetric methods are usually based on the following aspects: complex-formation reaction, Oxidation-reduction process and a catalytic effect.

Arancibia studied the effect of chitosan particles on periodontal pathogens and gingival fibroblasts.7 Chitosan inhibited the growth of Porphyromonasgingivalis and Aggregatibacteractinomycetemcomitans. Further the study revealed that chitosan exhibited predominantly anti-inflammatory activity by modulating the prostaglandin E2 levels.7This study showed that chitosan could be used in the prevention or treatment of periodontal inflammation. Akncbay et al., studied the use of chitosan gel in the treatment of chronic periodontitis.8 The study showed that chitosan itself is effective as an adjunct in the treatment of chronic periodontitis. Addition of metronidazole to the chitosan gel provides additional benefits.8

Chitosan has hemostatic properties, which helps in coagulation of blood by involving the platelets and rapid formation of the thrombus. Since chitosan has natural antibacterial properties, it can also be used as bandages or in wound dressings.Table 1 lists the other medical and dental uses of chitosan.

Conclusion:

Chitosan is biocompatible, has anti-inflammatory and anti-microbial properties. These properties make it a good vehicle for carrying active molecules to the periodontal diseased site. Chitosan based periodontal chips can be prepared easily, active drug molecules can be incorporated at desired concentrations for use in the prevention and treatment of periodontal disease.

References:

  1. Mlachkova AM, Popova CL. Efficiency of nonsurgical periodontal therapy inmoderate chronic periodontitis. Folia Med (Plovdiv). 2014;56(2):109-115.
  2. DiGangi P. Learning from biofilms. An overview, history, and the lessons they provide for the dental team. Dent Today. 2014;33(9):143-145.
  3. D. Marsh, A. Moter, and D. A. Devine, “Dental plaque biofilms: communities, conflict and control,” Periodontology 2000, 201155(1); 16–35.
  4. Hau H, Rohanizadeh R, Ghadiri M, Chrzanowski W. A mini-review on novel intraperiodontal pocket drug delivery materials for the treatment of periodontal diseases. Drug DelivTransl Res. 2014;4(3):295-301.
  5. Joshi D, Garg T, Goyal AK, Rath G. Advanced drug delivery approaches against periodontitis. Drug Deliv. 2014 Jul 9:1-15.
  6. Chitosan  accessed on 2/6/2015.
  7. Pichayakorn W, Boonme P. Evaluation of cross-linked chitosan microparticlescontaining metronidazole for periodontitis treatment. Mater SciEng C Mater Biol Appl. 2013;33(3):1197-1202.
  8. Arancibia R, Maturana C, Silva D, Tobar N, Tapia C, Salazar JC, Martínez J,Smith PC. Effects of chitosan particles in periodontal pathogens and gingival fibroblasts. J Dent Res. 2013;92(8):740-5.9.      Akncbay H, Senel S, Ay ZY Application of chitosan gel in the treatment of chronic periodontitis. J Biomed Mater Res B ApplBiomater. 2007;80(2):2906.;
  9. Akncbay H, Senel S, Ay ZY Application of chitosan gel in the treatment of chronic periodontitis. J Biomed Mater Res B ApplBiomater. 2007;80(2):2906.

More references are available on request.

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