Preparation and Evaluation of Metronidazole-Loaded Pectin Films for Potentially Targeting a Microbial Infection Associated with Periodontal Disease

Abstract

The objective of this study was to develop the metronidazole loaded high and low methoxyl pectin films (HM-G-MZ and LM-G-MZ) for the treatment of periodontal disease. The films were prepared by pectin 3% w/v, glycerin 40% w/v, and metronidazole 5% w/v. The developed films were characterized by scanning electron microscope and evaluated for thickness, weight variation, and elasticity. The developed films showing optimal mechanical properties were selected to evaluate radial swelling properties, in vitro release of metronidazole and the antimicrobial activity against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans by the disc diffusion method. The results demonstrated that LM-MZ and HM-G-MZ films were colorless and yellowish color, respectively, with the film thickness around 0.36–0.38 mm. Furthermore, both films exhibited good elasticity with low puncture strength (1.63 ± 0.37 and 0.84 ± 0.03 N/mm2, respectively) and also showed slight increase in radial swelling, so that they could be easily inserted and fitted into the periodontal pocket during a clinical use. However, HM-G-MZ showed a decrease in radial swelling after 1 h due to the film erosion. The in vitro release study of LM-G-MZ showed a burst release that was initially followed by a slow release rate profile, capable to maintain the therapeutic level in periodontal pocket for seven days, whereas HM-G-MZ showed an immediate release profile. The cumulative percentage of metronidazole release from HM-G-MZ was less than LM-G-MZ during the first 5 min as metronidazole was in a crystalline form inside HM-G-MZ film. For antimicrobial activity test, both films showed the inhibitory effect against P. gingivalis and A. actinomycetemcomitans, and there was no difference in the inhibition zone between LM-G-MZ and HM-G-MZ. The present study showed, for the first time, that low methoxyl pectin film containing glycerin and metronidazole could be potentially considered as a promising clinical tool for the drug delivery via intra-periodontal pocket to target an oral disease that is associated with polymicrobial infection.

Fabrication and Characterization of Low Methoxyl Pectin/Gelatin/Carboxymethyl Cellulose Absorbent Hydrogel Film for Wound Dressing Applications

“…All hydrogels were degassed and subsequently casted by pouring approximately 300 g onto the polycarbonate rectangular templates (17 cm length × 8.5 cm width). The hydrogel film was dried in an oven at 40 ± 2 °C for 48 h. Since calcium ions have been reported as crosslinkers in earlier studies for the preparation of LMP films [22,23], an optimized volume of 3% w/w CaCl 2 was poured on LMP/gelatin/CMC films in the templates. After 24 h, crosslinked films were taken out, and additionally washed with deionized water and then air-dried at room temperature for 24 h. After the drying step, translucent LMP/gelatin/CMC films were obtained.…”

“…Low methoxyl pectin (LMP) also has several unique properties that have enabled it to be used as a matrix with its distinction in water absorption and retention properties, hence known as superabsorbents [18,19,20]. Furthermore, crosslinked polymers derived from LMP can be used as a matrix for entrapment and/or delivery of a variety of drugs [21], including metronidazole [22]. Thus, our main goal of this study was to seek an optimal formulation of hydrogel film used to deliver povidone iodine.…”

Polymer-Based Systems for Controlled Release and Targeting of Drugs

“…For use in human applications, the polymer must primarily be biocompatible and non-toxic, and then functionalizable to give the appropriate structural and functional characteristics, such as to make it easily workable, processed, and engineered to obtain the desired system, and to be applied in drug delivery and targeting and/or in diagnosis of diseases.The further possibility of decorating the surface of these polymeric systems (due to the characteristics of the material that constitutes the matrix) with ligands capable of interacting specifically with membrane receptors on cells represents a unique advantage for obtaining targeted drug release to a specific organ, tissue, or cell type [3][4][5][6][7].In this issue, some current examples of design and production of polymeric materials, as well as of searching strategies to modify existing ones, for the making of innovative systems for drug delivery and/or regenerative medicine are collected.In particular, polymeric systems from nanoscale (micelles [8,9], nanoparticles [10,11]) to microscale structures (microparticles [12,13]), and to macrodevices (hydrogels [14] and films [15]) were produced. All the described systems were designed for the controlled and targeted release of conventional or biological drugs, such as paclitaxel [10], or siRNA [11] in the treatment of diseases such as cancer [8] and buccal and skin infections [15,16] by the systemic or local administration route [17]. The starting polymeric materials were chosen from hydrophilic polysaccharides [11,16] to hydrophobic polyesters [9,14], obtaining blended materials or copolymers, which were used to obtain drug delivery systems by using techniques such as microfluidics or hot punching [12,13].Polymeric porous microparticles are currently emerging due to their potential for various applications, such as floating drug delivery systems and inhaled formulations.…”

“…In particular, polymeric systems from nanoscale (micelles [8,9], nanoparticles [10,11]) to microscale structures (microparticles [12,13]), and to macrodevices (hydrogels [14] and films [15]) were produced. All the described systems were designed for the controlled and targeted release of conventional or biological drugs, such as paclitaxel [10], or siRNA [11] in the treatment of diseases such as cancer [8] and buccal and skin infections [15,16] by the systemic or local administration route [17]. The starting polymeric materials were chosen from hydrophilic polysaccharides [11,16] to hydrophobic polyesters [9,14], obtaining blended materials or copolymers, which were used to obtain drug delivery systems by using techniques such as microfluidics or hot punching [12,13].…”

“…Marto and coworkers described a new approach to treat superficial skin infections by topical application of antibiotics, such as minocycline hydrochloride, formulated in a novel starch-based Pickering emulsion [16]. Junmahasathien and coworkers described the realization of pectin films, loaded with metronidazole, for the treatment of periodontal disease [15]. The preliminary results showed that low methoxyl pectin film containing glycerin and metronidazole could be potentially considered as a promising clinical tool for drug delivery via an intra-periodontal pocket to target an oral disease that is associated with polymicrobial infection.…”