Treatment Of Localized Periodontitis Research Articles

Osteogenesis promotion by injectable methacryloylated gelatin containing psoralen and its bacteriostatic properties.

The treatment of periodontitis focuses on controlling the progression of inflammation, reducing plaque accumulation, and promoting bone tissue reconstruction. Among them, the reconstruction of irregular bone resorption caused by periodontitis is a long-standing challenge. At present, the local drug treatment of periodontitis is mainly anti-inflammatory and antibacterial drugs. In this study, psoralen (Pso), a Chinese herbal medicine with anti-inflammatory, antibacterial, and osteogenic effects, was selected for the local treatment of periodontitis. Meanwhile, an injectable methacrylate gelatin (GelMA) platform loading with Pso was constructed. Pso-GelMA had the properties of fluidity, light cohesion, self-healing, and slow release, which could be better used in the deep and narrow structure of the periodontal pocket, and greatly increased the effectiveness of local drug delivery. The pore size of Gelma hydrogel did not change after loading Pso by SEM. In vitro, Pso-GelMA effectively upregulated the expression of osteogenic genes and proteins, increased alkaline phosphatase activity, promoted the mineralisation of rat bone marrow mesenchymal stem cells (BMSCs) extracellular matrix, and had significant antibacterial effects on Staphylococcus aureus and Fusobacterium nucleatum. Therefore, Pso-GelMA has immense promise in the adjuvant treatment of periodontitis.

In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with Doxycycline Hyclate for Topical Application in Periodontitis

Mucoadhesive films loaded with doxycycline hyclate (Doxy Hyc), consisting of mixtures of hydroxypropylmethyl cellulose (HPMC) E3, K4 and polyacrylic acid (Carbopol 940), were prepared by casting method, aiming to design a formulation intended for application in the oral cavity. The obtained film formulations exhibited a Doxy Hyc content between 7.52 ± 0.42 and 7.83 ± 0.41%, which had adequate mechanical properties for application in the oral cavity and pH values in the tolerance range. The x-ray diffraction studies highlighted the amorphisation of Doxy Hyc in the preparation process and the antibiotic particles present on the surface of the films, identified in the TEM images, which ensured a burst release effect in the first 15 min of the in vitro dissolution studies, after which Doxy Hyc was released by diffusion, the data presenting a good correlation with the Peppas model, n < 0.5. The formulation F1, consisting of HPMC K4 combined with C940 in a ratio of 5:3, the most performing in vitro, was tested in vivo in experimentally-induced periodontitis and demonstrated its effectiveness in improving the clinical parameters and reducing the salivary levels of matrix metalloproteinase-8 (MMP-8). The prepared Doxy Hyc loaded mucoadhesive buccal film could be used as an adjuvant for the local treatment of periodontitis, ensuring prolonged release of the antibiotic after topical application.

Coaxial electrospun nanofibers as drug delivery system for local treatment of periodontitis.

The aim of the present study was to prepare resorbable polylactide fibers for periodontitis treatment using coaxial electrospinning to optimize the release of metronidazole (MNA) by reducing the initial burst effect. Poly(L-lactide-co-D,L-lactide) (PLA) fibers mats with different distributions of metronidazole (MNA) were manufactured by coaxial electrospinning (COAX). By COAX spinning the central core of the fiber was enriched with 40% MNA (m/m), while the sheath of the fiber consisted of PLA only (test group). In contrast, fibers of the control group were prepared by conventional electrospinning with the same amount of MNA but with a homogenous drug distribution (HDD - homogenously distributed drug). The release of MNA was determined by analyzing aliquots from the fiber mats using UV-VIS spectroscopy. Agar diffusion tests were carried out to determine the antibacterial effect on periodontopathogenic bacteria. Biocompatibility was tested in direct contact to human gingival fibroblasts (HGF) for two days. The COAX mats showed a retarded drug release compared to the conventional HDD fibers. After 24h, 64% of total MNA was released cumulatively from the COAX fibers while 90% of the MNA was released from the HDD fibers (controls). The antibacterial effect of COAX fibers was significantly higher after 24h compared to the HDD fibers. Cell cultivation revealed significant higher numbers of vital cells among the COAX mats. COAX fibers showed improved sustained MNA release compared to conventional fibers and can be seen as potential drug delivery systems in local periodontitis treatment.

Interconnection of periodontal disease and comorbidities: Evidence, mechanisms, and implications.

Periodontitis, a microbiome-driven inflammatory disease of the tooth-attachment apparatus, is epidemiologically linked with other disorders, including cardio-metabolic, cognitive neurodegenerative and autoimmune diseases, respiratory infections, and certain cancers. These associations may, in part, be causal, as suggested by interventional studies showing that local treatment of periodontitis reduces systemic inflammation and surrogate markers of comorbid diseases. The potential cause-and-effect connection between periodontitis and comorbidities is corroborated by studies in preclinical models of disease, which additionally provided mechanistic insights into these associations. This overview discusses recent advances in our understanding of the periodontitis-systemic disease connection, which may potentially lead to innovative therapeutic options to reduce the risk of periodontitis-linked comorbidities.

Recombinant human PDGF-BB in combination with mineralized freeze-dried bone allograft in the treatment of Grade II furcation involvement: A case report

Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is commercially available biomaterial that can be used to regenerate the lost periodontal structure due to progression of periodontitis. The present case describes the surgical treatment of localized periodontitis with furcation Grade II involvement using platelet-derived growth factor BB (growth-factor enhanced matrix 21S) in combination with particulate allograft bone (mineralize freeze-dried bone allograft [FDBA]).This case report showed complete furcation closure after using rhPDGF-BB in combination with FDBA to treat localized periodontitis case with Grade II furcation involvement.

Performance of simvastatin microsponges as a local treatment for chronic periodontitis – Randomized clinical trial

Simvastatin (SV) is a lipid lowering drug exhibits anti-inflammatory and anabolic effects on the bone, so it could be utilized for the local treatment of periodontitis. However, the poor solubility of SV limits its penetration through the gingival sulcus. Encapsulating SV into microsponges may have the potential to enhance the dissolution and subsequently its local penetration. In this study, SV microsponges had been prepared using the emulsion-solvent evaporation technique where, Eudragit RS-100 was employed as the polymer. The % encapsulation efficiency(%EE) of drug approached 77.32 ± 2.03. The prepared microsponges were free flowing, spherical in shape having narrow size distribution range. The particle size of the prepared microsponges was 93.79 ± 7.21 μm in diameter with a small polydispersity index (PDI) of 0.0059 ± 0.0008. In-vitro dissolution studies of SV microsponges showed that the solubility of SV had significantly enhanced upon inclusion inside the microsponges. Fourier transform infrared (FT-IR) spectroscopy indicated hydrogen bond formation between SV and Eudragit RS-100. The prepared microsponges were incorporated in chitosan 2% gels. A clinical study was conducted on 24 selected patients having bony periodontal defects to compare the efficacy of chitosan 2% gel containing free (SV) with that containing SV microsponge in treatment of chronic periodontitis. Results showed that the chitosan gels containing SV microsponges exhibited significant reduction in both pocket depth and clinical attachment loss compared to those prepared with free SV. This might be attributed to hydrogen bond formation between microsponges entrapped SV and chitosan, thus microsponges are auspicious as a carrier for SV for local treatment of periodontitis.

Minocycline hydrochloride loaded mPEG-PCLA membranes: Preparation and in vitro evaluation for periodontitis therapy

This study was aimed at alleviating shortcomings in the treatment of periodontitis by preparation of a biopolymer membrane loaded with minocycline hydrochloride (MH) inserted into periodontal pockets to treat infections. Monomethoxy-poly (ethylene glycol)-poly (ε-caprolactone-co-L-lactide) (mPEG-PCLA) is a biocompatible and biodegradable amphiphilic block copolymer. It, therefore, has attracted considerable attention in drug delivery systems and periodontal treatment. We chose it as a membrane material for MH-drug loading. The MH-loaded membranes were prepared by the solvent casting technique with the content of 5, 8 and 10 wt.%, respectively. Fourier transform infrared spectra (FTIR) revealed no interaction between MH and polymer. The drug-loaded membrane surface morphology was investigated by scanning electron microscopy (SEM). In vitro release studies showed that the initial drug release exceeded 40% within 24 h, followed by a sustained release for up to 2 weeks, which would enable the therapeutic level to maintain over a longer time. The antibacterial activity studies in vitro demonstrated a positive effect on the periodontal pathogen. MH drug-loaded membranes have no adverse effect on the growth of periodontal ligament fibroblasts in the MTT test. The study suggests that mPEG-PCLA membranes containing MH are a potential antibacterial drug delivery system for local treatment of periodontitis.

Root extract and proanthocyanidins on oral bacteria viability - Nijole Savickiene

Elevated proportions of some subgingival microbial species have been associated with destructive periodontal disease activity. Biologically active compounds of Pelargonium sidoides root extract (PSRE) or Proanthocyanidins (PACNs) from this extract modulate bacterial virulence and stimulate host immune responses. There is no local delivery system of sustained release formulations with PSRE or PACNs available, however, bioactive capacities of these substances suggest them as promising prolonged local periodontitis treatment candidates.

Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities.

Periodontitis, a major inflammatory disease of the oral mucosa, is epidemiologically associated with other chronic inflammation-driven disorders, including cardio-metabolic, neurodegenerative and autoimmune diseases and cancer. Emerging evidence from interventional studies indicates that local treatment of periodontitis ameliorates surrogate markers of comorbid conditions. The potential causal link between periodontitis and its comorbidities is further strengthened by recent experimental animal studies establishing biologically plausible and clinically consistent mechanisms whereby periodontitis could initiate or aggravate a comorbid condition. This multi-faceted ‘mechanistic causality’ aspect of the link between periodontitis and comorbidities is the focus of this Review. Understanding how certain extra-oral pathologies are affected by disseminated periodontal pathogens and periodontitis-associated systemic inflammation, including adaptation of bone marrow haematopoietic progenitors, may provide new therapeutic options to reduce the risk of periodontitis-associated comorbidities.

Beta-cyclodextrin-based in situ forming micro-particle for intra-periodontal pocket antimicrobial drug delivery

Doxycycline hyclate (DH) is the drug of choice practically be administered for local periodontitis treatment. The DH-loaded in situ micro-particle (ISM) using beta cyclodextrin (β-CD) as the matrix base for intra-periodontal pocket drug delivery was focused in this study. The non-aqueous in oil injectable emulsion was prepared using a two-syringe connector system. The stable emulsion was obtained when the internal phase contained 5% w/w DH with 35% w/w β-CD dissolved in N-methyl pyrrolidone (NMP) and the external phase contained 7.5% w/w glycerol monostearate (GMS) dispersed in olive oil. The pH and viscosity of this system were 3.54 ± 0.14 and 207.03 ± 7.56 cPs, respectively, with a pseudo-plastic flow and suitable injectable manner for intra-periodontal injection. The transformation from emulsion into a DH-loaded β-CD micro-particle was rapid after contact with simulated crevicular fluid. The transformation rate was slightly higher than the solvent diffusion rate from the solvent exchange mechanism. The prolonged DH release from β-CD micro-particle was attained after tested with the dialysis tube method and showed efficient antimicrobial activities especially against Porphyromonas gingivalis. This investigation indicated the potential application of β-CD as the matrix for ISM for the development of local drug delivery system for periodontitis treatment.

In-situ forming implants for dual controlled release of chlorhexidine and ibuprofen for periodontitis treatment: Microbiological and mechanical key properties

In-situ forming implants (ISFI) which simultaneously release an antimicrobial and anti-inflammatory drug in a controlled manner offer an interesting potential for local periodontitis treatment. In this study, poly(lactic-co-glycolic acid) (PLGA)-based implants loaded with chlorhexidine and ibuprofen were investigated, in particular with respect to their antimicrobial and mechanical key properties. PLGA (Resomer RG 502H) was dissolved in N-methyl pyrrolidone (NMP). Chlorhexidine dihydrochloride and ibuprofen (free acid) were added as well as acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC, Methocel, E50) as adhesion enhancer. Upon contact with aqueous fluids, the NMP diffuses out and water into the formulation, causing polymer precipitation and drug entrapment. The antimicrobial activity against periodontal pathogens was studied using the agar-well diffusion test, time-kill studies and growth curve method. The syringeability of the liquid formulations and mechanical key properties of the in-situ formed implants were investigated using a texture analyzer. A commercially available gel used for local periodontitis treatment, loaded with chlorhexidine dihydrochloride and chlorhexidine digluconate (Chlo-site) was studied for reasons of comparison. Importantly, the investigated ISFIs showed a strong and rapid antibacterial activity against all the selected pathogens, while maintaining suitable mechanical properties. The simultaneous release of ibuprofen did not reduce the desired antimicrobial effect of chlorhexidine.

Therapeutic potential for insulin on type1 diabetes-associated periodontitis: Analysis of experimental periodontitis in streptozotocin-induced diabetic rats.

Aims/IntroductionThe association between diabetes and periodontal disease is considered to be bidirectional. However, there is still controversy surrounding the relationship between periodontal disease and type 1 diabetes. We investigated whether insulin improves periodontitis without any local treatments for periodontitis under type 1 diabetes conditions using the ligature‐induced experimental periodontitis model.Materials and MethodsType 1 diabetic rats were induced by streptozotocin injection. Experimental periodontitis was induced by ligature in normal and diabetic rats. Half of the diabetic rats were treated with insulin. Two weeks after the ligature, periodontitis was evaluated.ResultsInsulin treatment significantly improved inflammatory cell infiltration and inflammatory cytokine gene expression, leading to suppression of alveolar bone loss, in the periodontitis of diabetic rats. Insulin also suppressed the periodontitis‐increased nitric oxide synthase‐positive cells in periodontal tissue of the diabetic rats. Even without induction of periodontitis, diabetic rats showed decreased gingival blood flow and an increased number of nitric oxide synthase‐positive cells in the gingiva and alveolar bone loss compared with normal rats, all of which were ameliorated by insulin treatment. We further confirmed that insulin directly suppressed lipopolysaccharide‐induced inflammatory cytokine expressions in THP‐1 cells.ConclusionsThere were abnormalities of periodontal tissue even without the induction of periodontitis in streptozotocin‐induced diabetic rats. Insulin treatment significantly ameliorated periodontitis without local periodontitis treatment in diabetic rats. These data suggest the therapeutic impacts of insulin on periodontitis in type 1 diabetes.

The combined use of herbal remedies in patients with chronic periodontitis: experimental and applied aspects

Воспалительно-деструктивные заболевания пародонта являются одной из наиболее сложных и распространенных форм патологии и основной причиной потери зубов среди взрослого населения, поэтому разработка и внедрение новых лекарственных форм для лечения воспалительных заболеваний пародонта является актуальной задачей. Применяемые лекарственные средства растительного происхождения обладают разнообразными фармакологическими свойствами, которые могут быть полезными как антимикробные воздействия на биопленку или как иммуностимулирующие препараты. Целью работы стало обоснование эффективности растительных препаратов Тонзинал и фитопластин ЦМ-1 по результатам клинико-лабораторных исследований в биореакторе in vitro и при местном лечении пародонтита. Полученные результаты способствовали подтверждению эффективности комплексного применения препаратов растительного происхождения с целью пролонгации ремиссии заболевания, а также повышения качества оказываемой пародонтологической помощи.

Metronidazole-Loaded Porous Matrices for Local Periodontitis Treatment: In Vitro Evaluation and In Vivo Pilot Study

Periodontal therapy focuses on thorough removal of subgingival calculus and plaque products followed by the smoothing out of root surfaces. However, such conventional mechanotherapeutic approaches are inefficient with regard to microbial biofilm elimination from the space between the root and deep periodontal pockets. Therefore, local chemotherapeutic agents need to be applied. Local antimicrobial treatment is also considered a safer treatment, as it avoids systemic complications related to drug application. In this study, porous matrices consisting of gelatin (GE) and cellulose derivatives (carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC)) were loaded with antimicrobial drug metronidazole (MTZ). The matrices’ structural morphology, physiochemical properties, swelling and degradation ratio, mechanical properties, and MTZ release from the matrices were analyzed. Additionally, cytotoxicity tests for fibroblast and osteoblast cell cultures (L929 and U2-OS, respectively) and antimicrobial activity assessments of MTZ-loaded matrices against anaerobic Bacteroides sp. Bacteria were performed. Finally, clinical application of HEC matrices into periodontal pockets was conducted. The applied matrices showed a high antibacterial efficacy and a moderate cytotoxicity in vitro. The clinical application of HEC dressings corresponded with the decrease of periodontal pockets’ depth and bleeding observed 1 month after a single application. The presented results show that intra-pocket application of metronidazole using manufactured matrices may serve not only as a support for a standard treatment in periodontal practice but also as an alternative to systemic drug administration in this setting. Clinical data were analyzed using a nonparametric Friedman’s ANOVA for dependent trials.

ВЫЯВЛЕНИЕ И ЛЕЧЕНИЕ ЛОКАЛИЗОВАННОГО ПАРОДОНТИТА С РЕЦЕССИЕЙ ДЕСНЫ

This article fully describes the process of detection and treatment of localized periodontitis with recessionary gums. The analysis of the sources found among the scientific works and theses will allow to fully disclose the problem of treatment of periodontitis.

Treatment of localized periodontitis in persons with diabetes mellitus type 2 with use of gingival adhesive balm

Treatment of localized periodontitis in persons with diabetes mellitus type 2 with use of gingival adhesive balm

New Treatment for Dentistry Regeneration Based on Metronidazole Release from Collagen/Strontium Sponges

It is well known that periodontitis causes rapid destruction of gingival and bone tissues. Topical treatments are suitable because the drug can be delivered in a proper and controlled concentration. Metronidazole proved to be efficient for patients with aggressive periodontitis. By this study we aimed to obtain spongious drug delivery systems for local periodontitis treatment based on collagen, strontium renalate and metronidazole. Collagen spongious forms were obtained by lyophilisation of composite gels based on collagen:strontium ranelate (50:50) and different concentrations of metronidazole. The obtained spongious forms were characterized by FT-IR, water up-take, optic microscopy and in vitro release of metronidazole. The prepared matrices absorbed a maximum amount of water after 30 min. The most absorbent sample is the reference one (only collagen) which absorbed about 35% water; the adding of metronidazole decrease the water absorption due to its lipophilic behavior. The samples with strontium are more compact and they absorbed less water than the ones without strontium. Because the samples were not cross-linked they degrade during 24 hours of water absorption process. The drug percentage released was influenced by the drug and strontium ranelate concentrations. The analysis performed sponges indicate that these composites can be useful as drug delivery supports.

Effect of 1,25(OH)2 D3 and 20(OH)D3 on interleukin-1β-stimulated interleukin-6 and -8 production by human gingival fibroblasts.

Vitamin D-1,25(OH)2 D3 or 1,25D3-maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1. The objectives were to determine the effects of 1,25D3 or a non-calcemic analog, 20-hydroxyvitamin D3 -20(OH)D3 or 20D3-on IL-1β-stimulated IL-6 and IL-8 production, and NF-κB and MAPK/AP-1 activation, by human gingival fibroblasts. Human gingival fibroblasts were incubated ± IL-1β, with or without exposure to 1,25D3 or 20D3. IL-6 and IL-8 in culture supernatants were measured by enzyme-linked immunosorbent assay. NF-κB (p65) and AP-1 (phospho-cJun) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. IL-1β-stimulated IL-6 and IL-8 levels were both significantly inhibited (40%-60%) (P<.045) by 1,25D3, but not 20D3 (0%-15% inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited IL-1β-stimulated nuclear levels of p65 and phospho-cJun (P<.02). Reduction of the activation of NF-κB and AP-1 alone is not able to inhibit strongly the IL-1β stimulated IL-6 and IL-8 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors/processes/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.

Physical key properties of antibiotic-free, PLGA/HPMC-based in-situ forming implants for local periodontitis treatment

In-situ forming implants (ISFI) offer an interesting potential for the treatment of periodontitis, allowing for time-controlled drug release directly at the site of action (which is difficult to reach). For this purpose, ISFI loaded with antibiotics have been reported in the literature. But the use of antibiotic drugs at low doses over prolonged periods of time can lead to the development of bacterial resistances. This risk should be avoided. The aim of this study was to develop a novel type of in-situ forming implants, loaded with the antiseptic drug chlorhexidine. Special emphasis was placed on the physical properties of the systems, assuring a reliable residence time in the periodontal pockets of patients suffering from periodontitis. In particular, the risk of premature, accidental loss of the formulations due to mechanical stress (e.g. during tooth brushing and chewing) was to be reduced. Two commercially available drug products for local periodontitis treatment were studied for reasons of comparison: Chlo-site and Parocline. The syringeability and swelling behavior of the formulations were investigated, and the hardness, springiness, resilience and “stickiness” of the systems determined using extracted human teeth. Interestingly, the novel in-situ forming implants, based on PLGA/HPMC and being free of antibiotics, exhibit highly promising physical key properties: They are intensively sticking to teeth’ surfaces and provide adequate mechanical strength to assure reliable and prolonged residence times in periodontal pockets. In contrast, the commercial drug products showed limited adhesion and either rapidly shrank (Chlo-site), or substantially swelled and were mechanically very weak (Parocline).

An injectable in situ gel with cubic and hexagonal nanostructures for local treatment of chronic periodontitis

Periodontitis is a chronic bacterial infection, and its effective treatment is dependent on the retention of antibiotics of effective concentrations at the periodontal pockets. In this study, a solution–gel based inverse lyotropic liquid crystalline (LLC) system was explored to deliver metronidazole to the periodontal pockets for local treatment of periodontitis. It was found that the metronidazole-loaded LLC precursor spontaneously transformed into gel in the presence of water in the oral cavity. The low viscosity of the precursor would allow its penetration to the rather difficult to reach infection sites, while the adhesiveness and crystalline nanostructures (inverse bicontinuous cubic Pn3m phase and inverse hexagonal phase) of the formed gel would permit its firm adhesion to the periodontal pockets. The LLC system provided sustained drug release over one week in vitro. Results from in vivo study using a rabbit periodontitis model showed that the LLC system was able to maintain the metronidazole concentrations in the periodontal pockets above the minimum inhibition concentration for over 10 days without detectable drug concentration in the blood. Owing to the spontaneous solution–gel transition in the periodontal pockets and unique liquid crystalline nanostructures, the LLC in situ gel provided effective treatment of periodontitis for a prolonged period of time with reduced systematic side effects, compared to metronidazole suspension which was effective for 24 h with detectable metronidazole concentrations in the blood after 6 h.