Zinc Oxide Gels for Periodontitis Treatment

Jongjan Mahadlek1, Juree Charoenteeraboon2 and Thawatchai Phaechamud1* 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University,

Nakhon Pathom 73000, Thailand 2Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University,

Nakhon Pathom 73000, Thailand

*Corresponding Author: Tel. (034) 255-800, Fax. (034) 255-801, E-mail: jongjan.m@hotmail.com

Abstract

Periodontitis is a localized inflammation of

the periodontal pocket caused by bacterial

infection, which can result in tooth loss. The intra-

pocket drug delivery system was highly effective

for the treatment of periodontitis diseases. Zinc

oxide (ZnO) has been claimed as one of tooth

filling material and it can exhibit the antimicrobial

activity. Therefore, the prepared gels containing

ZnO were developed for the treatment of

periodontitis with the practical administration. ZnO

was studied as the main compound and xanthan

gum was used as the gel-forming agent. The effect

of clove oil and eugenol added into the prepared gel

were studied. The prepared gels were evaluated on

the gel properties including viscosity, pH and

antimicrobial activity. The viscosity of the prepared

gel was increased as the concentration of xanthan

gum, ZnO, clove oil and eugenol were increased.

The antimicrobial activity of the prepared gel was

increased when the concentration of clove oil was

increased. The antimicrobial activity of systems

comprising clove oil tended to be higher than that

of eugenol.

Keywords: Periodontitis, Zinc oxide, Xanthan gum,

Clove oil, Eugenol

1. Introduction

Periodontitis is an inflammatory disease of the teeth

supporting tissues caused by groups of specific

microorganisms. The current periodontal therapy

emphasizes to remove the bacterial and to shift the

pathogenic microbes to one compatible with

periodontal health. ZnO exhibited antibacterial and

antifungal activity [1]. Developed zinc oxide

eugenol cement (ZOE) has been widely used in

dentistry for indirect pulp capping, and as a

temporary filling and root canal sealer [2]. Xanthan

gum is a water-soluble polysaccharide produced by

Xanthomonas campestris. Xanthan gum has been

used as a viscosity inducing agent. Clove oil has

been reported for antimicrobial properties against

S. Enteritidis, E. coli and S. aureus. Eugenol, an

active principle of clove oil, is largely employed in

perfumes and mouthwashes and as dental analgesic.

It is used in the form of a paste or mixture as dental

cement, filler and restorative material. It is a known

antibacterial agent against pathogens including E.

coli, C. jejuni, S. aureus and H. pyroli [3].

The objective of this study was to develop an intra-

pocket delivery system for periodontitis treatment.

The polymer chosen for use in this study was

xanthan gum due to its unique gel-forming

property. ZnO, clove oil and eugenol has been

claimed for microbial inhibition thus they were

incorporated into the developed gel for periodontitis

treatment.

2. Methods

2.1 Preparation of xanthan gum gels

397

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The xanthan gum dispersions were prepared by

addition of required amount of gum into deionized

water under gradually stirring at room temperature

for 24 h. The concentrations of xanthan gum were

0.05, 0.1, 0.25, 0.5, 1.5, 2, 3 and 4 %w/w. The 2

%w/w xanthan gum containing ZnO (10, 15, 20, 25

and 30 %w/w) were prepared. Then the clove oil

and eugenol (0.5, 1, 3, 5, 10, 15� and 20 %w/w)

were added to the gel containing 2%w/w xanthan

gum and 20%w/w ZnO.

2.3 The pH and viscosity measurements

The pH of formulations was measured by a pH

meter (Professional Meter PP-15 Sartorius,

Goettingen, Germany) (n=3). The viscosity of the

prepared gels were determined using Brookfield

DV-III Ultra programmable rheometer (Brookfield

Engineering Laboratories.Inc., USA) (n=4).

2.3 Antimicrobial studies

Antimicrobial activity of the samples were tested

using the agar diffusion method. The standard

microbes were used in this study was

Staphylococcus aureus (ATCC 6538P). The

actively growing broth culture of microbes were

prepared, the turbidity was adjusted to be contain

approximately 108 cells/mL. Then, the swab

spreaded onto the agar plate and the spread culture

were to dry. The sterilized cylinder cups were

placed carefully on the surface of the swabbed agar.

The prepared gels were filled into the cylinder cup

and incubated at 37°C for 24 h. The antimicrobial

activities were measured as the diameter (cm) of

clear zone of growth inhibition (n=6).

3. Results and discussion

The viscosity of the gels were increased with the

concentration of xanthan gum (Fig.1). It has been

reported that concentration of polymer has

considerable effect on rheological characteristics of

xanthan gum. As concentration was increased, the

polysaccharides chains came more closer and then

their mutual entanglement were occurred [4]. ZnO

was added into the selected system containing

2%w/w xanthan gum. The viscosity of system

increased when the amount of ZnO was increased

(data not shown).

0

400

800

1200

1600

2000

0 0.5 1 1.5 2 2.5 3 3.5 4Concentration of xanthan gum (%w/w)

Vis

cosi

ty (

mP

as-1

)

Fig.1 Effect of xanthan gum on gel viscosity (n=4)

The viscosity of the prepared gel containing

2%w/w xanthan gum and 20%w/w ZnO was

increased as the concentration of clove oil was

increased as shown in Fig. 2. The viscosity of the

prepared gel increased as the concentration of

eugenol was increased up to 15%w/w (Fig. 3).

0

500

1000

1500

2000

2500

3000

0 2.5 5 7.5 10 12.5 15

Concentration of clove oil (%w/w)

Vis

cosi

ty (

mP

as-1

)

Fig.2 Effect of clove oil on gel viscosity (n=6)

0

500

1000

1500

2000

2500

0 2.5 5 7.5 10 12.5 15

Concentration of eugenol (%w/w)

Vis

cosi

ty (m

Pas

-1)

Fig.3 Effect of eugenol on gel viscosity (n=6)

398

�

The concentration of ZnO did not notably affect on

pH of aqueous system. The pH of systems were

between range 6.71 to 6.94. When the concentration

of clove oil and eugenol were increased, the pH of

the prepared gels were between range 7.41 to 7.97.

The growth inhibition of microbe S. aureus was

studied by agar-cup diffusion method. The prepared

gel containing 2%w/w xanthan gum, 20%w/w ZnO

and various the concentrations of clove oil or

eugenol were evaluated for the antimicrobial

activity. The antibacterial activity of the systems

were increased when the concentration of clove oil

and eugenol were increased (Table 1). As the

concentration of clove oil was increased,

antimicrobial activity was increased (p<0.05)

whereas the antimicrobial activity of system

containing different amounts of eugenol are not

different by statistical significance (data not

shown). Addition of clove oil tended to show the

higher antibacterial activity than that of eugenol but

from statistical analysis, the antibacterial activity of

the system containing the same concentration of

clove oil and eugenol are not different by statistical

significance (data not shown). However, this result

was corresponding to the antimicrobial activity of

clove oil and eugenol alone, which clove oil

exhibited higher antibacterial against S. aureus than

eugenol. Since clove oil has several interesting

active compounds including eugenol. Therefore the

Table 1 Effect of concentration of clove oil and

eugenol on antimicrobial activity (n=6)

Concentration Clove oil Eugenol

Inhibition zone (cm.) (%w/w)

mean + SD mean + SD

1 0.00 + 0.00 0.00 + 0.00 3 1.00 + 0.00 1.05 + 0.07 5 1.15 + 0.07 1.20 + 0.00

10 1.35 + 0.21 1.30 + 0.14 15 1.75 + 0.07 1.30 + 0.28

prepared gel containing xanthan gum (2%w/w),

ZnO (20%w/w) and clove oil (15%w/w) was

selected to use as formulation for periodontitis

treatment.

4. Conclusions�

The gels for periodontitis treatment were prepared

and evaluated. The xanthan gum in the preparation

was used as gel-forming agent. For this study, the

suitable gel for periodontitis treatment contained

xanthan gum (2%w/w), ZnO (20%w/w) and clove

oil (15%w/w).

Acknowledgments

This work was kindly supported by the Faculty of

Pharmacy, Silpakorn University.

References

1. Cassanho, A. C. A., Fernandes, A. M. F., Oliveira L.

D., Carvalho, C. A. T., Jorge, A. O. C. and Ito, C. Y.

K., “In vitro activity of zinc oxide-eugenol and glass

ionomer cements on Candida albicans”, Brazilian

Oral Research, 19(2): 134-138 (2005).

2. Fernandez, O. I., Chacon, E. And Irabien, A.,

“Influence of lead, zinc, iron (III) and chromium

(III) oxides on the setting time and strength

development of Portland cement”, Cement and

Concrete Research, 31: 1213–1219 (2001).

3. Walsh, S. E., Maillard, J. Y., Russell, A. D.,

Catrenich, C. E., Charbonneau, D. L. and Bartolo, R.

G., “Activity and mechanisms of action of selected

biocidal agents on Gram- positive and negative

bacteria”, Journal of Applied Microbiology, 94(2):

240–247 (2003).

4. Ahmed, J. and Ramaswamy, H. S., “Effect of high-

hydrostatic pressure and concentration on

rheological characteristics of xanthan gum”, Food

Hydrocolloids, 18: 367–373 (2004).

399

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CONTENTS

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