Development and Evaluation of Biodegradable Chitosan Films of Metronidazole and Levofloxacin for the Management of Periodontitis

The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl2 concentrations, whereas zeta potential depends only on the Alg and CaCl2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (−9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm−1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model (R2 between 0.956–0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.

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“…cm −1 (C-C stretching), 1534 and 1366 cm −1 (nitroso N-O stretch), and 1075, 875 cm −1 (C-N stretch) [47].…”

Section: Ftir Spectroscopic Analysis Of Cs-algnps and Met-cs-algnpsmentioning

confidence: 98%

A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design

et al. 2020

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“…Ofloxacin loaded poly (methacrylic acid) and hydroxypropyl-cellulose strips were reported by Kimura et al [134]. Gayasuddin et al designed an intra-pocket, biodegradable film of chitosan loaded with metronidazole and levofloxacin meant for inserting into periodontal pockets to treat infections, and it demonstrated sustained release for up to seven days [120]. These studies show that the application of DDS in periodontal pockets had significant therapeutic effects for periodontitis.…”

Section: Anti-bacterial Dds For Periodontitismentioning

confidence: 93%

“…Nowadays, various antimicrobial agents have been loaded into different dosage forms to prolong their persistence time in periodontal tissue. Tetracycline group antibiotics, including doxycycline hydrochloride [36,117,125], tetracycline [132,133], and minocycline [122,124]; nitroimidazoles antibiotics like metronidazole [116,120] and tinidazole [55] are mostly used. Other antibiotics like quinolones have also been reported (Figure 5a).…”

Section: Anti-bacterial Dds For Periodontitismentioning

confidence: 99%

Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment

et al. 2020

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The oral cavity is a unique complex ecosystem colonized with huge numbers of microorganism species. Oral cavities are closely associated with oral health and sequentially with systemic health. Many factors might cause the shift of composition of oral microbiota, thus leading to the dysbiosis of oral micro-environment and oral infectious diseases. Local therapies and dental hygiene procedures are the main kinds of treatment. Currently, oral drug delivery systems (DDS) have drawn great attention, and are considered as important adjuvant therapy for oral infectious diseases. DDS are devices that could transport and release the therapeutic drugs or bioactive agents to a certain site and a certain rate in vivo. They could significantly increase the therapeutic effect and reduce the side effect compared with traditional medicine. In the review, emerging recent applications of DDS in the treatment for oral infectious diseases have been summarized, including dental caries, periodontitis, peri-implantitis and oral candidiasis. Furthermore, oral stimuli-responsive DDS, also known as "smart" DDS, have been reported recently, which could react to oral environment and provide more accurate drug delivery or release. In this article, oral smart DDS have also been reviewed. The limits have been discussed, and the research potential demonstrates good prospects.Molecules 2020, 25, 516 2 of 29 problems. For example, systemic antibiotics such as tetracycline, beta-lactam antibiotics, nitroimidazoles have been used, especially in cases of periodontal diseases and peri-implantitis [12]. However, systemic antibiotics could cause problems like drug resistance, dysbacteriosis, and systemic side effects [13,14]. The antibacterial effect is also limited as very little could arrive at the oral lesion area after systemic circulation [15][16][17]. Fluoride in drinking water has been used for the prevention of dental caries but might cause excessive intake, leading to fluorosis [18]. Therefore, local drug therapy is now more considered for oral infectious diseases [19,20]. However, the conventional forms of local therapy, like drug suspension or rinse of anti-infection agents, could be easily washed off and thus could not last long in the oral cavity. Complex local lesions like deep periodontal pockets and teeth fissure are also difficult to reach. In order to improve the effect of prophylaxis and treatment, more precise targeting therapy is quite essential [21,22]. Therefore, drug delivery systems have drawn great attention in recent decades in oral infectious diseases. Drug delivery systems (DDS) are devices that can transport and release the therapeutic agents or bioactive substances to certain sites at certain rates in vivo [23,24], usually composed of the carriers and associated therapeutics [25]. They have been widely explored in biomedical research. With local drug administration and controlled drug release, DDS could provide higher curative efficiency and fewer side effects [23,26,27]. With all these advantages, DDS has been reported w...

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“…Metronidazole (MD) is nitroimodazole compound that has been widely used for treating infections caused by anaerobic bacteria and otitis media [1][2][3][4][5]. The nitro group of MD is activated by nitroreductases such as ferredoxin in the body.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Radiation Cross-Linked Poly(Acrylic Acid) Hydrogel Containing Metronidazole with Enhanced Antibacterial Activity

Jeong

Park

Kim

et al. 2019

IJMS

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Metronidazole (MD) is known as a periodontitis medicine and has been widely used in antibiotics for resistance to anaerobic bacteria, periodontal disease, and other threats. To treat diseases, drug delivery carriers are needed with a high bioadhesive property and enhanced drug penetration. Poly (acrylic acid) (PAA) hydrogel films have a good bioadhesive property and are able to localize the absorption site and increase the drug residence time. In this study, we fabricated a MD loaded PAA hydrogel with different MD content (0.1, 0.25, 0.5, and 1 wt%) using varying doses (25, 50, and 75 kGy) and the radiation doses (25, 50, or 75 kGy) in a one-step gamma-ray irradiation process. The chemical and physical structure were determined through a Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy, gel content, and compressive strength. In addition, MD loaded PAA hydrogels were performed to MD release behaviors and cytotoxicity. Finally, we conducted antibacterial activity to demonstrate the prevention of growth of bacteria as a therapeutic dressing. The basic chemical structure analysis of MD was changed greatly at radiation doses of 50 and 75 kGy due to degradation by gamma-ray irradiation. However, when the absorbed dose was 25 kGy, the chemical structure analysis of MD did not change significantly, and the gel content and compressive strength of MD/PAA hydrogel were approximately 80% and 130 kPa, respectively. The MD/PAA hydrogels exhibited no cytotoxicity and good antibacterial activity against Escherichia coli, Staphylococcus aureus, and Streptococcus mutans. These results provide good evidence that MD/PAA hydrogel prepared by gamma-ray irradiation has potential as a competitive candidate for the therapeutic dressing.

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Development and Evaluation of Biodegradable Chitosan Films of Metronidazole and Levofloxacin for the Management of Periodontitis

Cited by 70 publications

References 33 publications

A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design

A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design

Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment

Preparation of Radiation Cross-Linked Poly(Acrylic Acid) Hydrogel Containing Metronidazole with Enhanced Antibacterial Activity

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