Pharmaceutics

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14 pages, 4588 KiB

Open AccessArticle

Use of a Cellulase from Trichoderma reesei as an Adjuvant for Enterococcus faecalis Biofilm Disruption in Combination with Antibiotics as an Alternative Treatment in Secondary Endodontic Infection

by Selene Velázquez-Moreno, Ana Maria González-Amaro, Antonio Aragón-Piña, Lluvia Itzel López-López, Roberto Sánchez-Sánchez, Mario Alberto Pérez-Díaz, Ricardo Oliva Rodríguez, Ana C. Lorenzo-Leal, Omar González-Ortega, Fidel Martinez-Gutierrez and Horacio Bach

Pharmaceutics 2023, 15(3), 1010; https://doi.org/10.3390/pharmaceutics15031010 - 21 Mar 2023

Cited by 5 | Viewed by 2648

Abstract

Apical periodontitis is an inflammation leading to the injury and destruction of periradicular tissues. It is a sequence of events that starts from root canal infection, endodontic treatment, caries, or other dental interventions. Enterococcus faecalis is a ubiquitous oral pathogen that is challenging [...] Read more.

Apical periodontitis is an inflammation leading to the injury and destruction of periradicular tissues. It is a sequence of events that starts from root canal infection, endodontic treatment, caries, or other dental interventions. Enterococcus faecalis is a ubiquitous oral pathogen that is challenging to eradicate because of biofilm formation during tooth infection. This study evaluated a hydrolase (CEL) from the fungus Trichoderma reesei combined with amoxicillin/clavulanic acid as a treatment against a clinical E. faecalis strain. Electron microscopy was used to visualize the structure modification of the extracellular polymeric substances. Biofilms were developed on human dental apices using standardized bioreactors to evaluate the antibiofilm activity of the treatment. Calcein and ethidium homodimer assays were used to evaluate the cytotoxic activity in human fibroblasts. In contrast, the human-derived monocytic cell line (THP-1) was used to evaluate the immunological response of CEL. In addition, the secretion of the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine IL-10 were measured by ELISA. The results demonstrated that CEL did not induce the secretion of IL-6 and TNF-α when compared with lipopolysaccharide used as a positive control. Furthermore, the treatment combining CEL with amoxicillin/clavulanic acid showed excellent antibiofilm activity, with a 91.4% reduction in CFU on apical biofilms and a 97.6% reduction in the microcolonies. The results of this study could be used to develop a treatment to help eradicate persistent E. faecalis in apical periodontitis. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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17 pages, 11717 KiB

Open AccessArticle

Artemisinin Loaded Cerium-Doped Nanopowders Improved In Vitro the Biomineralization in Human Periodontal Ligament Cells

by Ioannis Tsamesidis, Anna Theocharidou, Anastasia Beketova, Maria Bousnaki, Iason Chatzimentor, Georgia K. Pouroutzidou, Dimitrios Gkiliopoulos and Eleana Kontonasaki

Pharmaceutics 2023, 15(2), 655; https://doi.org/10.3390/pharmaceutics15020655 - 15 Feb 2023

Cited by 4 | Viewed by 1921

Abstract

Background: A promising strategy to enhance bone regeneration is the use of bioactive materials doped with metallic ions with therapeutic effects and their combination with active substances and/or drugs. The aim of the present study was to investigate the osteogenic capacity of human [...] Read more.

Background: A promising strategy to enhance bone regeneration is the use of bioactive materials doped with metallic ions with therapeutic effects and their combination with active substances and/or drugs. The aim of the present study was to investigate the osteogenic capacity of human periodontal ligament cells (hPDLCs) in culture with artemisinin (ART)-loaded Ce-doped calcium silicate nanopowders (NPs); Methods: Mesoporous silica, calcium-doped and calcium/cerium-doped silicate NPs were synthesized via a surfactant-assisted cooperative self-assembly process. Human periodontal ligament cells (hPDLCs) were isolated and tested for their osteogenic differentiation in the presence of ART-loaded and unloaded NPs through alkaline phosphatase (ALP) activity and Alizarine red S staining, while their antioxidant capacity was also evaluated; Results: ART promoted further the osteogenic differentiation of hPDLCs in the presence of Ce-doped NPs. Higher amounts of Ce in the ART-loaded NPs inversely affected the mineral deposition process by the hPDLCs. ART and Ce in the NPs have a synergistic role controlling the redox status and reducing ROS production from the hPDLCs; Conclusions: By monitoring the Ce amount and ART concentration, mesoporous NPs with optimum properties can be developed towards bone tissue regeneration demonstrating also potential application in periodontal tissue regeneration strategies. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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15 pages, 2073 KiB

Open AccessArticle

Antimicrobial Peptides Active in In Vitro Models of Endodontic Bacterial Infections Modulate Inflammation in Human Cardiac Fibroblasts

by Giulia Marianantoni, Giada Meogrossi, Eva Tollapi, Alessandro Rencinai, Jlenia Brunetti, Crystal Marruganti, Carlo Gaeta, Alessandro Pini, Luisa Bracci, Marco Ferrari, Simone Grandini and Chiara Falciani

Pharmaceutics 2022, 14(10), 2081; https://doi.org/10.3390/pharmaceutics14102081 - 29 Sep 2022

Cited by 3 | Viewed by 2258

Abstract

Endodontic and periodontal disease are conditions of infectious origin that can lead to tooth loss or develop into systemic hyperinflammation, which may be associated with a wide variety of diseases, including cardiovascular. Endodontic and periodontal treatment often relies on antibiotics. Since new antimicrobial [...] Read more.

Endodontic and periodontal disease are conditions of infectious origin that can lead to tooth loss or develop into systemic hyperinflammation, which may be associated with a wide variety of diseases, including cardiovascular. Endodontic and periodontal treatment often relies on antibiotics. Since new antimicrobial resistances are a major threat, the use of standard antibiotics is not recommended when the infection is only local. Antimicrobial peptides were recently demonstrated to be valid alternatives for dental treatments. The antimicrobial peptide M33D is a tetrabranched peptide active against Gram-negative and Gram-positive bacteria. It has a long life, unusual for peptides, because its branched form provides resistance to proteases. Here the efficacy of M33D and of its analog M33i/l as antibiotics for local use in dentistry was evaluated. M33D and M33i/l were active against reference strains and multidrug-resistant clinical isolates of Gram-negative and Gram-positive species. Their minimum inhibitory concentration against different strains of dental interest was between 0.4 and 6.0 μM. Both peptides acted rapidly on bacteria, impairing membrane function. They also disrupted biofilm effectively. Disinfection of the root canal is crucial for endodontic treatments. M33D and M33i/l reduced E. faecalis colonies to one-twentieth in a dentin slices model reproducing root canal irrigation. They both captured and neutralized lipopolysaccharide (LPS), a bacterial toxin responsible for inflammation. The release of IL-1β and TNFα by LPS-stimulated murine macrophages was reduced by both peptides. Human cardiac fibroblasts respond to different insults with the release of proinflammatory cytokines, and consequently, they are considered directly involved in atherogenic cardiovascular processes, including those triggered by infections. The presence of M33D and M33i/l at MIC concentration reduced IL6 release from LPS- stimulated human cardiac fibroblasts, hence proving to be promising in preventing bacteria-induced atherogenesis. The two peptides showed low toxicity to mammalian cells, with an EC50 one order of magnitude higher than the average MIC and low hemolytic activity. The development of antimicrobial peptides for dental irrigations and medication is a very promising new field of research that will provide tools to fight dental infections and their severe consequences, while at the same time protecting standard antibiotics from new outbreaks of antimicrobial resistance. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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22 pages, 6811 KiB

Open AccessArticle

Fabrication and Optimization of Essential-Oil-Loaded Nanoemulsion Using Box–Behnken Design against Staphylococos aureus and Staphylococos epidermidis Isolated from Oral Cavity

by Niamat Ullah, Adnan Amin, Rana A. Alamoudi, Sheikh Abdur Rasheed, Ruaa A. Alamoudi, Asif Nawaz, Muhammad Raza, Touseef Nawaz, Saiqa Ishtiaq and Syed Shakil Abbas

Pharmaceutics 2022, 14(8), 1640; https://doi.org/10.3390/pharmaceutics14081640 - 5 Aug 2022

Cited by 19 | Viewed by 3892

Abstract

Oral bacterial infections are fairly common in patients with diabetes mellitus; however, due to limited treatment options, herbal medicines are considered an alternate solution. This study aimed to formulate a stable essential-oil-loaded nanoemulsion for the treatment of oral bacterial infections. Essential oils from [...] Read more.

Oral bacterial infections are fairly common in patients with diabetes mellitus; however, due to limited treatment options, herbal medicines are considered an alternate solution. This study aimed to formulate a stable essential-oil-loaded nanoemulsion for the treatment of oral bacterial infections. Essential oils from edible sources including coriander, clove, cinnamon and cardamom were extracted by hydrodistillation. The response surface methodology was used to optimize the nanoemulsion formulation by applying the Box–Behnken design. The oil concentration, surfactant concentration and stirring speed were three independent factors, and particle size and polydispersity index were two responses. The particle size, polydispersity index and zeta potential of the optimized formulation were 130 mm, 0.222 and −22.9, respectively. The ATR-FTIR analysis revealed that there was no incompatibility between the active ingredients and the excipients. A significant release profile in active ingredients of nanoemulsion, i.e., 88.75% of the cinnamaldehyde and 89.33% of eugenol, was recorded after 24 h. In the ex vivo goat mucosal permeation study, 71.67% of the cinnamaldehyde permeated and that of the eugenol 70.75% from the nanoemulsion. The optimized formulation of the essential-oil-loaded nanoemulsion showed a 9 mm zone of inhibition against Staphylococcus aureus and Staphylococcus epidermidis, whereas in anti-quorum sensing analysis, the optimized nanoemulsion formulation showed an 18 mm zone of inhibition. It was concluded that formulated essential-oil-loaded nanoemulsion can be used against S. epidermidis and S. aureus infections in oral cavity. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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14 pages, 2548 KiB

Open AccessArticle

High Molecular Weight Hyaluronic Acid Reduces the Expression of Virulence Genes fimA, mfa1, hagA, rgpA, and kgp in the Oral Pathogen Porphyromonas gingivalis

by Meshal S. Alharbi and Fahad A. Alshehri

Pharmaceutics 2022, 14(8), 1628; https://doi.org/10.3390/pharmaceutics14081628 - 4 Aug 2022

Cited by 8 | Viewed by 2359

Abstract

Porphyromonas gingivalis (P. gingivalis) is a cornerstone pathogen in the development and progression of periodontal and peri-implant tissue destruction. It is capable of causing dysbiosis of the microbial biofilm and modulation of the host immune system. Hyaluronic acid (HA) is a [...] Read more.

Porphyromonas gingivalis (P. gingivalis) is a cornerstone pathogen in the development and progression of periodontal and peri-implant tissue destruction. It is capable of causing dysbiosis of the microbial biofilm and modulation of the host immune system. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan found in all living organisms. It is well known and has been used for improving tissue healing. In addition, some studies have suggested that there may be an antimicrobial potential to HA. The aim of this study was to evaluate the effect of hyaluronic acid, azithromycin (AZM), and chlorhexidine (CHX) on the expression of genes (i.e., fimA, mfa1, hagA, rgpA, rgpB, and kgp) related to the virulence and adhesion of P. gingivalis. The study groups were divided into four: (1) HA treated group; (2) AZM treated group; (3) CHX treated group; and (4) untreated group to serve as a negative control. P. gingivalis ATCC 33277 was cultured and then exposed to four different concentrations (100% MIC, 50% MIC, 25% MIC, and 12.5% MIC) of HA, AZM, and CHX for 24 h. The expression levels of the aforementioned genes were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Relative fold-change values were calculated and compared between groups. The fold-change values of all genes combined were 0.46 ± 0.33, 0.31 ± 0.24, and 0.84 ± 0.77 for HA, AZM, and CHX, respectively. HA has downregulated all the genes by mostly a half-fold: 0.35 ± 0.20, 0.47 ± 0.35, 0.44 ± 0.25, 0.67 ± 0.46, 0.48 ± 0.33 and 0.35 ± 0.22 with fimA, mfa1, hagA, rgpA, rgpB and kgp, respectively. The effect of HA was significant on all genes except rgpB compared to the untreated control. Lower concentrations of HA tended to exhibit greater downregulation with 1 mg/mL being the most effective. High molecular weight (1.5 MDa) hyaluronic acid has a potent effect on P. gingivalis by downregulating fimA, mfa1, hagA, rgpA, and kgp. The effect of HA was generally less than that of AZM but greater than that of CHX. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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15 pages, 2687 KiB

Open AccessArticle

Potential Combinatory Effect of Cannabidiol and Triclosan Incorporated into Sustained Release Delivery System against Oral Candidiasis

by Mark Feldman, Irith Gati, Ronit Vogt Sionov, Sharonit Sahar-Helft, Michael Friedman and Doron Steinberg

Pharmaceutics 2022, 14(8), 1624; https://doi.org/10.3390/pharmaceutics14081624 - 3 Aug 2022

Cited by 5 | Viewed by 2245

Abstract

Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility [...] Read more.

Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility of incorporating CBD and/or triclosan (an antimicrobial agent that is widely utilized in dentistry) in a sustained-release varnish (SRV) (SRV-CBD, SRV-triclosan) to increase their pharmaceutical potential against C. albicans biofilm, as well as that of the mixture of the agents into SRV (SRV-CBD/triclosan). The study was conducted in a plastic model, on agar, and in an ex vivo tooth model. Our results demonstrated strong antibiofilm activity of SRV-CBD and SRV-triclosan against C. albicans in all tested models. Both formulations were able to inhibit biofilm formation and to remove mature fungal biofilm. In addition, SRV-CBD and SRV-triclosan altered C. albicans morphology. Finally, we observed a dramatic enhancement of antibiofilm activity when combined SRV-CBD/triclosan was applied. In conclusion, we propose that incorporation of CBD or triclosan into SRV is an effective strategy to fight fungal biofilms. Importantly, the data demonstrate that our CBD/triclosan varnish is safe, and is not cytotoxic for normal mammalian cells. Furthermore, we propose that CBD and triclosan being in mixture in SRV exhibit complementary antibiofilm activity, and thus can be explored for further development as a potential treatment against fungal infections. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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14 pages, 4098 KiB

Open AccessArticle

Trans-Cinnamaldehyde Eluting Porous Silicon Microparticles Mitigate Cariogenic Biofilms

by Afreen Jailani, Shanthini Kalimuthu, Vidhyashree Rajasekar, Sumanta Ghosh, Pierre-Yves Collart-Dutilleul, Naveen Fatima, Hyun Koo, Adline Princy Solomon, Frederic Cuisinier and Prasanna Neelakantan

Pharmaceutics 2022, 14(7), 1428; https://doi.org/10.3390/pharmaceutics14071428 - 7 Jul 2022

Cited by 4 | Viewed by 1940

Abstract

Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, [...] Read more.

Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, the remarkable difficulty in delivering such hydrophobic bioactive molecules prevents further development. To address this critical challenge, we have developed an innovative platform composed of components with a proven track record of safety. We fabricated and thoroughly characterised porous silicon (pSi) microparticles to carry and deliver the natural phenyl propanoid trans-cinnamaldehyde (TC). We investigated its effects on preventing the development of cross-kingdom biofilms (Streptococcus mutans and Candida albicans), typical of dental caries found in children. The prepared pSi microparticles were roughly cubic in structure with 70–75% porosity, to which the TC (pSi-TC) was loaded with about 45% efficiency. The pSi-TC particles exhibited a controlled release of the cargo over a 14-day period. Notably, pSi-TC significantly inhibited biofilms, specifically downregulating the glucan synthesis pathways, leading to reduced adhesion to the substrate. Acid production, a vital virulent trait for caries development, was also hindered by pSi-TC. This pioneering study highlights the potential to develop the novel pSi-TC as a dental caries-preventive material. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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14 pages, 6760 KiB

Open AccessArticle

New Autonomous Water-Enabled Self-Healing Coating Material with Antibacterial-Agent-Releasing Properties

by Ki-Hak Kim, Hang-Nga Mai, Dong-Choon Hyun and Du-Hyeong Lee

Pharmaceutics 2022, 14(5), 1005; https://doi.org/10.3390/pharmaceutics14051005 - 7 May 2022

Cited by 7 | Viewed by 2117

Abstract

A new autonomous water-enabled self-healing coating with antibacterial-agent-releasing capability was developed for the first time by precipitating an aqueous solution of hydrogen-bonded tannic acid (TA) and polyethylene glycol (PEG) (TA: 5 mg/mL; PEG: 5 mg/mL with M_W = 100 kDa) to form [...] Read more.

A new autonomous water-enabled self-healing coating with antibacterial-agent-releasing capability was developed for the first time by precipitating an aqueous solution of hydrogen-bonded tannic acid (TA) and polyethylene glycol (PEG) (TA: 5 mg/mL; PEG: 5 mg/mL with M_W = 100 kDa) to form a smooth, uniform coating layer with an average roughness of 0.688 nm and thickness of 22.3 μm on a polymethyl methacrylate (PMMA) substrate after 10 min of incubation. Our method is cost- and time-efficient, as the hydrophilic coating (water contact angle = 65.1°) forms rapidly, binding strongly to the PMMA substrate (adhesive energy = 83 mJ/m²), without the need for pretreatment or surface modification, and is capable of rapid self-repair (approximately 5 min) through hydrogen bonding in aqueous media. Furthermore, adding 0.5 mg/mL of chlorhexidine acetate (CHX), a commonly used antibacterial agent in dentistry, into the TA–PEG emulsion allowed the release of 2.89 μg/mL of the drug from the coating layer, which is promising for actively inhibiting the vitality and growth of bacteria around PMMA dental restorations. The use of CHX-loaded TA–PEG hydrogen-bonded complexes is highly favorable for the fabrication of an autonomous self-healing biocoating with active antibacterial-agent-releasing capability, which can be applied not only in dentistry but also in other medical fields. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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11 pages, 1901 KiB

Open AccessArticle

The Products of Probiotic Bacteria Effectively Treat Persistent Enterococcus faecalis Biofilms

by Shatha Safadi, Harsh Maan, Ilana Kolodkin-Gal, Igor Tsesis and Eyal Rosen

Pharmaceutics 2022, 14(4), 751; https://doi.org/10.3390/pharmaceutics14040751 - 30 Mar 2022

Cited by 9 | Viewed by 2632

Abstract

Objectives: Enterococcus faecalis is a Gram-positive commensal bacterium that possesses various survival and virulence factors, including the ability to compete with other microorganisms, invade dentinal tubules, and resist nutritional deprivation. E. faecalis is associated with persistent endodontic infections where biofilms formed by [...] Read more.

Objectives: Enterococcus faecalis is a Gram-positive commensal bacterium that possesses various survival and virulence factors, including the ability to compete with other microorganisms, invade dentinal tubules, and resist nutritional deprivation. E. faecalis is associated with persistent endodontic infections where biofilms formed by this bacterium in the root canal frequently resist dental therapies. Aseptic techniques, such as the inclusion of sodium hypochlorite, are the most commonly used methods to treat E. faecalis infections within the root canal system. In this work, we assess the effectiveness of probiotic strains to prevent the regrowth of E. faecalis biofilm cells treated by sodium hypochlorite irrigation. Methods: First, methods are presented that evaluate the effects of short-term exposure to sodium-hypochlorite on established E. faecalis. Next, we evaluate the effects of the secreted products of probiotic strains on biofilm cells and planktonic cells. Results: Sodium hypochlorite, the treatment conventionally used to decontaminate infected root canal systems, was extremely toxic to planktonic bacteria but did not fully eradicate biofilm cells. Furthermore, low concentrations of sodium hypochlorite induced eDNA dependent biofilms. Strikingly, conditioned medium from the probiotic bacteria Lactobacillus plantarum and Lactobacillus casei was sufficient to fully prevent the regrowth of treated biofilms while showing reduced potency towards planktonic cells. Conclusion: Sodium hypochlorite irrigations may contribute to the persistence of biofilm cells if used at concentrations lower than 3%. Probiotic strains and their products represent a new reservoir of biofilm therapies for E. faecalis infections formed in the root canal system. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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14 pages, 2325 KiB

Open AccessArticle

Embedding a Sensitive Liquid-Core Waveguide UV Detector into an HPLC-UV System for Simultaneous Quantification of Differently Dosed Active Ingredients during Drug Release

by Rebecca Chamberlain, Hellen Windolf, Bjoern B. Burckhardt, Jörg Breitkreutz and Björn Fischer

Pharmaceutics 2022, 14(3), 639; https://doi.org/10.3390/pharmaceutics14030639 - 14 Mar 2022

Cited by 6 | Viewed by 3492

Abstract

Individual dosing of pharmaceutics and personalized medicine have become important with regard to therapeutic safety. Dose adjustments, biorelevant drug release and combination of multiple active substances in one dosage form for the reduction in polymedication are essential aspects that increase the safety and [...] Read more.

Individual dosing of pharmaceutics and personalized medicine have become important with regard to therapeutic safety. Dose adjustments, biorelevant drug release and combination of multiple active substances in one dosage form for the reduction in polymedication are essential aspects that increase the safety and acceptance of the patient’s pharmacotherapy. Therefore, not only innovative drug products but also new analytical methods are needed during the drug development phase and for quality control that can simultaneously determine different active ingredients and cover wide concentration ranges. We investigated a liquid-core waveguide UV absorbance flow cell detector coupled to an existing HPLC-UV system. A Teflon AF 2400 capillary tubing of 20 cm length was connected in series to the HPLC flow line and enabled a lower limit of quantification of 1 ng/mL pramipexole (increase in sensitivity by 20 compared to common 0.9 cm flow cells). This allowed the low-concentration of pramipexole and the higher concentrations of levodopa and benserazide occurring during drug release to be determined in a single chromatographic run within 22.5 min. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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Review

Jump to: Research

23 pages, 3204 KiB

Open AccessReview

Local Delivery and Controlled Release Drugs Systems: A New Approach for the Clinical Treatment of Periodontitis Therapy

by Mariacristina Amato, Simona Santonocito, Alessandro Polizzi, Gianluca Martino Tartaglia, Vincenzo Ronsivalle, Gaia Viglianisi, Cristina Grippaudo and Gaetano Isola

Pharmaceutics 2023, 15(4), 1312; https://doi.org/10.3390/pharmaceutics15041312 - 21 Apr 2023

Cited by 24 | Viewed by 4768

Abstract

Periodontitis is an inflammatory disease of the gums characterized by the degeneration of periodontal ligaments, the formation of periodontal pockets, and the resorption of the alveolar bone, which results in the destruction of the teeth’s supporting structure. Periodontitis is caused by the growth [...] Read more.

Periodontitis is an inflammatory disease of the gums characterized by the degeneration of periodontal ligaments, the formation of periodontal pockets, and the resorption of the alveolar bone, which results in the destruction of the teeth’s supporting structure. Periodontitis is caused by the growth of diverse microflora (particularly anaerobes) in the pockets, releasing toxins and enzymes and stimulating the immune system. Various approaches, both local and systemic, have been used to treat periodontitis effectively. Successful treatment depends on reducing bacterial biofilm, bleeding on probing (BOP), and reducing or eliminating pockets. Currently, the use of local drug delivery systems (LDDSs) as an adjunctive therapy to scaling and root planing (SRP) in periodontitis is a promising strategy, resulting in greater efficacy and fewer adverse effects by controlling drug release. Selecting an appropriate bioactive agent and route of administration is the cornerstone of a successful periodontitis treatment plan. In this context, this review focuses on applications of LDDSs with varying properties in treating periodontitis with or without systemic diseases to identify current challenges and future research directions. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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18 pages, 788 KiB

Open AccessReview

Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents

by Simona Santonocito, Martina Donzella, Pietro Venezia, Giada Nicolosi, Rodolfo Mauceri and Gaetano Isola

Pharmaceutics 2023, 15(4), 1193; https://doi.org/10.3390/pharmaceutics15041193 - 9 Apr 2023

Cited by 3 | Viewed by 3820

Abstract

Pain is the most common symptom that dentists are confronted with, whether acute (pulpitis, acute periodontitis, post-surgery, etc.) or chronic diseases, such as periodontitis, muscle pain, temporomandibular joint (TMJ) disorders, burning mouth syndrome (BMS), oral lichen planus (OLP) and others. The success of [...] Read more.

Pain is the most common symptom that dentists are confronted with, whether acute (pulpitis, acute periodontitis, post-surgery, etc.) or chronic diseases, such as periodontitis, muscle pain, temporomandibular joint (TMJ) disorders, burning mouth syndrome (BMS), oral lichen planus (OLP) and others. The success of therapy depends on the reduction in and management of pain through specific drugs, hence the need to analyze new pain medications with specific activity, which are suitable for long-term use, with a low risk of side effects and interactions with other drugs, and capable of leading to a reduction in orofacial pain. Palmitoylethanolamide (PEA) is a bioactive lipid mediator, which is synthesized in all tissues of the body as a protective pro-homeostatic response to tissue damage and has aroused considerable interest in the dental field due to its anti-inflammatory, analgesic, antimicrobial, antipyretic, antiepileptic, immunomodulatory and neuroprotective activities. It has been observed that PEA could play a role in the management of the pain of orofacial origin, including BMS, OLP, periodontal disease, tongue a la carte and temporomandibular disorders (TMDs), as well as in the treatment of postoperative pain. However, actual clinical data on the use of PEA in the clinical management of patients with orofacial pain are still lacking. Therefore, the main objective of the present study is to provide an overview of orofacial pain in its many manifestations and an updated analysis of the molecular pain-relieving and anti-inflammatory properties of PEA to understand its beneficial effects in the management of patients with orofacial pain, both neuropathic and nociceptive in nature. The aim is also to direct research toward the testing and use of other natural agents that have already been shown to have anti-inflammatory, antioxidant and pain-relieving actions and could offer important support in the treatment of orofacial pain. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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18 pages, 2347 KiB

Open AccessReview

Drugs for the Quorum Sensing Inhibition of Oral Biofilm: New Frontiers and Insights in the Treatment of Periodontitis

by Alessandro Polizzi, Martina Donzella, Giada Nicolosi, Simona Santonocito, Paolo Pesce and Gaetano Isola

Pharmaceutics 2022, 14(12), 2740; https://doi.org/10.3390/pharmaceutics14122740 - 7 Dec 2022

Cited by 10 | Viewed by 5141

Abstract

Chemical molecules are used by microorganisms to communicate with each other. Quorum sensing is the mechanism through which microorganisms regulate their population density and activity with chemical signaling. The inhibition of quorum sensing, called quorum quenching, may disrupt oral biofilm formation, which is [...] Read more.

Chemical molecules are used by microorganisms to communicate with each other. Quorum sensing is the mechanism through which microorganisms regulate their population density and activity with chemical signaling. The inhibition of quorum sensing, called quorum quenching, may disrupt oral biofilm formation, which is the main etiological factor of oral diseases, including periodontitis. Periodontitis is a chronic inflammatory disorder of infectious etiology involving the hard and soft periodontal tissues and which is related to various systemic disorders, including cardiovascular diseases, diabetes and obesity. The employment of adjuvant therapies to traditional scaling and root planing is currently being studied to further reduce the impact of periodontitis. In this sense, using antibiotics and antiseptics involves non-negligible risks, such as antibiotic resistance phenomena and hinders the re-establishment of eubiosis. Different quorum sensing signal molecules have been identified in periodontal pathogenic oral bacteria. In this regard, quorum sensing inhibitors are emerging as some interesting solutions for the management of periodontitis. Therefore, the aim of this review is to summarize the current state of knowledge on the mechanisms of quorum sensing signal molecules produced by oral biofilm and to analyze the potential of quorum sensing inhibitors for the management of periodontitis. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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18 pages, 1713 KiB

Open AccessReview

Advanced Drug Delivery Platforms for the Treatment of Oral Pathogens

by Seyed Ebrahim Alavi, Aun Raza, Max Gholami, Michael Giles, Rayan Al-Sammak, Ali Ibrahim, Hasan Ebrahimi Shahmabadi and Lavanya A. Sharma

Pharmaceutics 2022, 14(11), 2293; https://doi.org/10.3390/pharmaceutics14112293 - 26 Oct 2022

Cited by 13 | Viewed by 2249

Abstract

The oral cavity is a complex ecosystem accommodating various microorganisms (e.g., bacteria and fungi). Various factors, such as diet change and poor oral hygiene, can change the composition of oral microbiota, resulting in the dysbiosis of the oral micro-environment and the emergence of [...] Read more.

The oral cavity is a complex ecosystem accommodating various microorganisms (e.g., bacteria and fungi). Various factors, such as diet change and poor oral hygiene, can change the composition of oral microbiota, resulting in the dysbiosis of the oral micro-environment and the emergence of pathogenic microorganisms, and consequently, oral infectious diseases. Systemic administration is frequently used for drug delivery in the treatment of diseases and is associated with the problems, such as drug resistance and dysbiosis. To overcome these challenges, oral drug delivery systems (DDS) have received considerable attention. In this literature review, the related articles are identified, and their findings, in terms of current therapeutic challenges and the applications of DDSs, especially nanoscopic DDSs, for the treatment of oral infectious diseases are highlighted. DDSs are also discussed in terms of structures and therapeutic agents (e.g., antibiotics, antifungals, antiviral, and ions) that they deliver. In addition, strategies (e.g., theranostics, hydrogel, microparticle, strips/fibers, and pH-sensitive nanoparticles), which can improve the treatment outcome of these diseases, are highlighted. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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14 pages, 936 KiB

Open AccessReview

Curcumin as a Natural Approach of Periodontal Adjunctive Treatment and Its Immunological Implications: A Narrative Review

by Sorina Mihaela Solomon, Celina Silvia Stafie, Irina-Georgeta Sufaru, Silvia Teslaru, Cristina Mihaela Ghiciuc, Florin Dumitru Petrariu and Oana Tanculescu

Pharmaceutics 2022, 14(5), 982; https://doi.org/10.3390/pharmaceutics14050982 - 3 May 2022

Cited by 7 | Viewed by 3235

Abstract

Scaling and root planing represent the gold standard in the treatment of periodontal disease, but these therapeutic methods cannot eliminate the remaining periodontopathogenic bacteria in cement, tubules, and periodontal soft tissue. Thus, a number of additional therapeutic means have been adopted, including local [...] Read more.

Scaling and root planing represent the gold standard in the treatment of periodontal disease, but these therapeutic methods cannot eliminate the remaining periodontopathogenic bacteria in cement, tubules, and periodontal soft tissue. Thus, a number of additional therapeutic means have been adopted, including local and systemic antibiotic therapy, as well as the use of photodynamic therapy techniques. Recently, special attention has been paid to potential phytotherapeutic means in the treatment of periodontal disease. In this review, we aim to present the effects generated by the extract of Curcuma longa, the various forms of application of turmeric as an additional therapeutic means, as well as the aspects related to its biotolerance. Full article

(This article belongs to the Special Issue Drug Delivery and Pharmacokinetics in Oral Medicine and Dental Infection)

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