## 4 Discussion  
In the present study was evaluated physicochemical and biological properties of metronidazole-loaded polymer matrices. Based on the obtained results, formulation with HEC was chosen for clinical assessment after one month as an adjunct to scaling and root planning in the management of periodontitis. In pilot-study mean pocket depth after one week and four weeks, the durations of the study were \(4.33\pm 2.16\) mm and \(3.98\pm 1.94\) mm, respectively, for the test group (Table 8). Mean reduction in pocket depth from baseline were \(0.55\pm 0.76\) mm and \(0.90\pm 0.89\) mm for the duration of the study at one week and four weeks, respectively. Our results are in accordance with those of [PERSON] et al. [46] and [PERSON] et al. [47], who found a statistically significant difference in mean pocket depth reduction between the scaling and root planning group and chlorhexidine chip-treated group. Reductions in the bleeding index score at the one-week and four-week intervals were \(5.0\pm 0.65\) and \(9.0\pm 0.77\), respectively, for the test group as compared with baseline (Table 7). There was a statistically significant difference in the bleeding index score observed at one week and four weeks compared with baseline. These findings are in accordance with those of [PERSON] et al., who found a mean reduction in bleeding index score at one month compared with baseline after application of controlled-release delivery of chlorhexidine gluconate.  
\begin{table}
\begin{tabular}{c c c c} \hline  & **Test 1** & **Test 2** & **Test 3** \\ \hline Mean API & 54 & 32 & 26 \\ mean BOP & 25 & 20 & 16 \\ mean PBI & 3.14 & 1.71 & 1.21 \\ \hline \end{tabular}
\end{table}
Table 7: Clinical pilot study results. API - Approximal Plaque Index, BOP—Bleeding on Probing, PBI—Papilla Bleeding Index.  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multicolumn{4}{c}{**Friedman ANOVA and Kendall Coeff of Concordance ANOVA**} \\  & **Chi Sqr (n = 84, df = 4) = 231.032** \\ \(p\) = 0.0000, Coeff of Concordance = 0.69057, Aver Rank r = 0.68684** \\ \hline
**Variable** & **Average Rank** & **Sum of Ranks** & **Mean** & **Std Dev** \\ \hline Pocket depth & 3.089286 & 259.5000 & 4.88095 & 2.39681 \\ No. & 4.767857 & 400.5000 & 42.5000 & 24.39262 \\ Pretest & 3.089286 & 259.5000 & 4.88095 & 2.39681 \\ After 1 week & 2.244048 & 188.5000 & 4.33333 & 2.16952 \\ After 4 weeks & 1.809524 & 152.0000 & 3.98810 & 1.94809 \\ \hline \end{tabular} ANOVA, analysis of variance; Coeff, coefficient; Chi Sqr, chi-square; Std Dev, standard deviation.  
\end{table}
Table 8: The Friedman ANOVA Test.  
[PERSON] et al. [48] compared clinical effects of topical application of metronidazolezole-coated nanofibers in periodontal pockets as an adjunct to scaling and root planning in periodontitis on a 7-patient group. The mean reductions of pocket depth after two weeks in that study were 1.8 mm and 2.4 mm in scaling alone and scaling in combination with adjunctronidazolezole-coated nanofibers, respectively. However, our matrices offer advantages such as biodegradability, high biocompatibility, uncoadhesive properties, hemostatic properties, lack of organic solvents used to preparing, and comfortable application in comparison to other synthetic drug carriers, i.e., nanofibers.  
In summary, we conclude that the in-pocket application of metronidazolezole is a worthwhile supplementation of the classical periodontal inflammation treatment and a feasible alternative to the use of antibiotics in periodontal diseases. As the single application of MTZ results in improvement of the clinical condition are comparable to the standard method, further research is recommended in order to test other treatment protocols.