Search Results (28)

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

Cellulose acetate butyrate (CAB) and cellulose acetate propionate (CAP) are biobased materials that are insoluble in water and present a potential alternative to fossil-based plastics. Solvent removal-induced in situ matrices are gaining attention as an innovative dosage form for localized drug delivery for periodontitis therapy. This study aims to develop levofloxacin hemihydrate (Lh)-loaded in situ matrices formed through solvent removal, incorporating various molecular weights (MWs) and concentrations of CAB and CAP. Increased MWs and higher concentrations of these cellulosic esters significantly improved formulation viscosity and injection force, contributing to enhanced phase inversion and greater matrix toughness. Microscopic analysis of interfacial phase changes revealed progressive thickening of the matrix over time, which was influenced by polymer concentration and limited solvent movement. The transformed matrices with high MW CAP and elevated CAB content demonstrated prolonged drug release, predominantly following first-order kinetics, suggesting drug dissolution and diffusion through the scaffold structure. CAB-based in situ matrices containing 15% and 20% polymer exhibited low viscosities suitable for injection, along with optimal gel formation for maintaining their shape, and adhered effectively to periodontal pockets. These matrices provided extended Lh release for up to 120 h and inhibited the growth of periodontopathic bacteria for over 15 days. Therefore, the developed Lh-loaded in situ matrices show promise as an effective treatment for periodontitis, warranting further research to explore their therapeutic potential. Full article

Cellulose acetate butyrate is a biodegradable cellulose ester bioplastic produced from plentiful natural plant-based resources. Solvent-exchange-induced in situ gels are particularly promising for periodontitis therapy, as this dosage form allows for the direct delivery of high concentrations of antimicrobial agents to the localized periodontal pocket. This study developed an in situ gel for periodontitis treatment, incorporating a combination of metronidazole and doxycycline hyclate, with cellulose acetate butyrate serving as the matrix-forming agent. Consequently, assessments were conducted on the physicochemical properties, gel formation, drug permeation, drug release, morphological topography, and antimicrobial activities of the formulation. The formulation demonstrated an increased slope characteristic of Newtonian flow at higher bioplastic concentrations. The adequate polymer concentration facilitated swift phase inversion, resulting in robust, solid-like matrices. The mechanical characteristics of the transformed in situ gel typically exhibit an upward trend as the polymer concentration increased. The utilization of sodium fluorescein and Nile red as fluorescent probes effectively tracked the interfacial solvent–aqueous movement during the phase inversion of in situ gels, confirming that the cellulose acetate butyrate matrix delayed the solvent exchange process. The initial burst release of metronidazole and doxycycline hyclate was minimized, achieving a sustained release profile over 7 days in in situ gels containing 25% and 40% cellulose acetate butyrate, primarily governed by a diffusion-controlled release mechanism. Metronidazole showed higher permeation through the porcine buccal membrane, while doxycycline hyclate exhibited greater tissue accumulation, both influenced by polymer concentration. The more highly concentrated polymeric in situ gel formed a uniformly porous structure. Metronidazole and doxycycline hyclate-loaded in situ gels showed synergistic antibacterial effects against S. aureus and P. gingivalis. Over time, the more highly concentrated polymeric in situ gel showed superior retention of antibacterial efficacy due to its denser cellulose acetate butyrate matrix, which modulated drug release and enhanced synergistic effects, making it a promising injectable treatment for periodontitis, particularly against P. gingivalis. Full article

Periodontitis is a chronic inflammation caused by periodontopathogenic bacteria in the dental biofilm, and also involves the inflammatory-immune response of the host. Polymorphonuclear neutrophils (PMNs) play essential roles in bacterial clearance by multiple mechanisms, including the formation of neutrophil extracellular traps (NETs) that retain and destroy pathogens. During PD progression, the interaction between PMNs, NETs, and bacteria leads to an exaggerated immune response and a prolonged inflammatory state. As a lesion matures, PMNs accumulate in the periodontal tissues and die via NETosis, ultimately resulting in tissue injury. A better understanding of the role of NETs, the associated molecules, and the pathogenic pathways of NET formation in periodontitis, could provide markers of NETosis as reliable diagnostic and prognostic tools. Moreover, an assessment of NET biomarker levels in biofluids, particularly in saliva or gingival crevicular fluid, could be useful for monitoring periodontitis progression and treatment efficacy. Preventing excessive NET accumulation in periodontal tissues, by both controlling NETs’ formation and their appropriate removal, could be a key for further development of more efficient therapeutic approaches. In periodontal therapy, local drug delivery (LDD) systems are more targeted, enhancing the bioavailability of active pharmacological agents in the periodontal pocket and surrounding tissues for prolonged time to ensure an optimal therapeutic outcome. Full article

Delivery systems for biologically active substances such as proanthocyanidins (PCANs), produced in the form of electrospun nonwoven through the electrospinning method, were designed using a polymeric blend of poly(L-lactide-co-glycolide) (PLGA)and poly[(R,S)-3-hydroxybutyrate] ((R,S)-PHB). The studies involved the structural and thermal characteristics of the developed electrospun three-dimensional fibre matrices unloaded and loaded with PCANs. In the next step, the hydrolytic degradation tests of these systems were performed. The release profile of PCANs from the electrospun nonwoven was determined with the aid of UV–VIS spectroscopy. Approximately 30% of the PCANs were released from the tested electrospun nonwoven during the initial 15–20 days of incubation. The chemical structure of water-soluble oligomers that were formed after the hydrolytic degradation of the developed delivery system was identified through electrospray ionization mass spectrometry. Oligomers of lactic acid and OLAGA oligocopolyester, as well as oligo-3-hydroxybutyrate terminated with hydroxyl and carboxyl end groups, were recognized as degradation products released into the water during the incubation time. It was also demonstrated that variations in the degradation rate of individual mat components influenced the degradation pattern and the number of formed oligomers. The obtained results suggest that the incorporation of proanthocyanidins into the system slowed down the hydrolytic degradation process of the poly(L-lactide-co-glycolide)/poly[(R,S)-3-hydroxybutyrate] three-dimensional fibre matrix. In addition, in vitro cytotoxicity and antimicrobial studies advocate the use of PCANs for biomedical applications with promising antimicrobial activity. Full article

Zeolites and zeolitic imidazolate frameworks (ZIFs) are crystalline aluminosilicates with porous structure, which are closely linked with nanomaterials. They are characterized by enhanced ion exchange capacity, physical–chemical stability, thermal stability and biocompatibility, making them a promising material for dental applications. This review aimed to provide an overview of the application of zeolites and ZIFs in dentistry. The common zeolite compounds for dental application include silver zeolite, zinc zeolite, calcium zeolite and strontium zeolite. The common ZIFs for dental application include ZIF-8 and ZIF-67. Zeolites and ZIFs have been employed in various areas of dentistry, such as restorative dentistry, endodontics, prosthodontics, implantology, periodontics, orthodontics and oral surgery. In restorative dentistry, zeolites and ZIFs are used as antimicrobial additives in dental adhesives and restorative materials. In endodontics, zeolites are used in root-end fillings, root canal irritants, root canal sealers and bone matrix scaffolds for peri-apical diseases. In prosthodontics, zeolites can be incorporated into denture bases, tissue conditioners, soft denture liners and dental prostheses. In implantology, zeolites and ZIFs are applied in dental implants, bone graft materials, bone adhesive hydrogels, drug delivery systems and electrospinning. In periodontics, zeolites can be applied as antibacterial agents for deep periodontal pockets, while ZIFs can be embedded in guided tissue regeneration membranes and guided bone regeneration membranes. In orthodontics, zeolites can be applied in orthodontic appliances. Additionally, for oral surgery, zeolites can be used in oral cancer diagnostic marker membranes, maxillofacial prosthesis silicone elastomer and tooth extraction medicines, while ZIFs can be incorporated to osteogenic glue or used as a carrier for antitumour drugs. In summary, zeolites have a broad application in dentistry and are receiving more attention from clinicians and researchers. Full article

Naturally sourced products like propolis are commonly employed for the non-surgical treatment of periodontal pockets. The use of nanoparticle formulations of these natural remedies has the potential to improve treatment outcomes. The aim of the present study was to evaluate the efficacy of sub-gingivally delivered propolis nanoparticles in the non-surgical management of periodontal pockets. Forty patients diagnosed with periodontitis presenting at least one periodontal pocket with a probing pocket depth between 4 and 6 mm were selected. Patients were randomly assigned into the control group (n = 20), which received scaling and root planing (SRP) and saline (SRP + Saline), and the test group (n = 20), which received SRP and sub-gingivally delivered propolis nanoparticles (PRO) into the periodontal pocket (SRP + PRO). The clinical parameters recorded were plaque index (PI), gingival index (GI), relative attachment loss (RAL), probing pocket depth (PPD), and bleeding on probing (BOP). They were assessed at baseline, one month, and three months post therapy. The results indicated that there was a significant improvement in clinical parameters (p < 0.05) in the test sites compared with the control sites at the end of the study. The gingival index at one month and three months was found to be significantly better in the SRP + PRO group than the SRP + Saline group, with a p value of <0.001. The BOP, PPD, and RAL showed significant improvement with the SRP + PRO group at the end of the 3-month follow-up with p values of 0.0001, 0.001, and 0.05, respectively. The subgingival delivery of propolis nanoparticles showed promising results as an adjunct to SRP in patients with periodontitis presenting periodontal pockets. Full article

The development of effective drug delivery systems remains a focus of extensive research to enhance therapeutic outcomes. Among these, in situ forming gels (ISG) have emerged as a promising avenue for controlled drug release. This research focuses on the mathematical modeling of levofloxacin HCl (Lv) release from zein-based ISG using the cup method, aiming to mimic the environment of a periodontal pocket. The drug release behavior of the ISGs was investigated through experimental observations and numerical simulations employing forward and central difference formula. Notably, the experimental data for drug release from the 20% w/w zein-based ISG formulations closely aligned with the simulations obtained from numerical mechanistic modeling. In summary, 20% w/w zein-based ISG formulations demonstrated nearly complete drug release with the maximum drug concentration at the edge of the matrix phase values consistently around 100–105%, while 25% w/w zein-based ISG formulations exhibited somewhat lower drug release extents, with values ranging from 70–90%. Additionally, the rate of drug transport from the polymer matrix to the external phase influenced initial release rates, resulting in a slower release. The utilization of glycerol formal as a solvent extended drug release further than dimethyl sulfoxide, thanks to denser matrices formed by high-loading polymers that acted as robust barriers to solvent removal and drug diffusion. Furthermore, UV-vis imaging was utilized to visualize the matrix formation process and solvent diffusion within the ISGs. The imaging results offered valuable insights into the matrix formation kinetics, controlled drug release mechanisms, and the influence of solvent properties on drug diffusion. The combination of mathematical modeling and experimental visualization provides a comprehensive understanding of drug release from zein-based ISGs and offers a foundation for tailored drug delivery strategies. Full article

Endo-periodontal lesions are challenging clinical situations where both the supporting tissues and the root canal of the same tooth are infected. In the present study, chlorhexidine (CHX)-loaded calcium hydroxide (CH) pastes were used as intracanal medications (ICMs). They were prepared and tested on pathogens found in both the root canal and the periodontal pocket. Exposure to 0.5% and 1% CHX-loaded ICMs decreased the growth of Porphyromonas gingivalis and was effective in eradicating or inhibiting an Enterococcus faecalis biofilm. CH was injected into the root canal of extracted human teeth immersed in deionized water. CHX-loaded ICMs resulted in the transradicular diffusion of active components outside the tooth through the apex and the lateral dentinal tubules, as shown by the release of CHX (from 3.99 µg/mL to 51.28 µg/mL) and changes in pH (from 6.63 to 8.18) and calcium concentrations (from 2.42 ppm to 14.67 ppm) after 7 days. The 0.5% CHX-loaded ICM was non-toxic and reduced the release of IL-6 by periodontal cells stimulated by P. gingivalis lipopolysaccharides. Results indicate that the root canal may serve as a reservoir for periodontal drug delivery and that CHX-based ICMs can be an adjuvant for the control of infections and inflammation in endo-periodontal lesions. Full article

Placing antimicrobial treatments directly in periodontal pockets is an example of the local administration of antimicrobial drugs to treat periodontitis. This method of therapy is advantageous since the drug concentration after application far surpasses the minimum inhibitory concentration (MIC) and lasts for a number of weeks. As a result, numerous local drug delivery systems (LDDSs) utilizing various antibiotics or antiseptics have been created. There is constant effort to develop novel formulations for the localized administration of periodontitis treatments, some of which have failed to show any efficacy while others show promise. Thus, future research should focus on the way LDDSs can be personalized in order to optimize future clinical protocols in periodontal therapy. Full article

Solvent exchange-induced in situ forming gel (ISG) has emerged as a versatile drug delivery system, particularly for periodontal pocket applications. In this study, we developed lincomycin HCl-loaded ISGs using a 40% borneol-based matrix and N-methyl pyrrolidone (NMP) as a solvent. The physicochemical properties and antimicrobial activities of the ISGs were evaluated. The prepared ISGs exhibited low viscosity and reduced surface tension, allowing for easy injection and spreadability. Gel formation increased the contact angle on agarose gel, while higher lincomycin HCl content decreased water tolerance and facilitated phase separation. The drug-loading influenced solvent exchange and matrix formation, resulting in thinner and inhomogeneous borneol matrices with slower gel formation and lower gel hardness. The lincomycin HCl-loaded borneol-based ISGs demonstrated sustained drug release above the minimum inhibitory concentration (MIC) for 8 days, following Fickian diffusion and fitting well with Higuchi’s equation. These formulations exhibited dose-dependent inhibition of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 8739, and Prophyromonas gingivalis ATCC 33277, and the release of NMP effectively inhibited Candida albicans ATCC 10231. Overall, the 7.5% lincomycin HCl-loaded 40% borneol-based ISGs hold promise as localized drug delivery systems for periodontitis treatment. Full article

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

Modulation with the suppression of infection and inflammation is essential to the successful treatment of periodontitis. An aqueous insoluble hydrophobic anti-inflammatory compound, i.e., ibuprofen (IBU), was investigated in this study as the matrix-forming agent of a doxycycline hyclate (DH)-loaded solvent removal-induced in situ forming gel (ISG) using dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) as the solvents. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, injectability, mechanical properties, gel formation, and drug release, were determined. Their antimicrobial activities were tested using agar cup diffusion, and their anti-inflammatory activity was assessed using thermal inhibition of protein denaturation of egg albumin. Increasing the IBU content decreased the density, pH, surface tension, and contact angle but increased the viscosity, force and work of injection, and gel formation of IBU-based ISG solution. Although their water tolerance values decreased with the increase in IBU content, the addition of DH and the use of NMP led to high water tolerance. The characterization of the dried gel remnants of ISGs presented no change in IBU crystallinity and thermal properties and confirmed no chemical interaction among the components of ISGs. The obtained transformed IBU matrix prolonged the release of DH and IBU from ISGs over 7 days from its tortuously packed IBU matrix with small pores, and conformed well with Fickian diffusion mechanism. The developed DH-loaded solvent removal-induced IBU-based ISGs exhibited efficient antimicrobial activities against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Candida albicans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. IBU in formulation promoted the antimicrobial activity of ISGs, whereas DH and NMP promoted the anti-inflammatory activity of ISGs. Consequently, the DH-loaded solvent removal-induced IBU-based ISGs proposed in this study show great potential as an effective bioactive drug delivery system for periodontitis treatment by localized periodontal pocket injection. Full article

Local delivery of drugs or antimicrobial agents is a suitable approach in the management of periodontitis when the infection is localized deep in the pockets and does not adequately respond to mechanical debridement and/or systemic antibiotic treatment. In this context, the objective of this study was to prepare new biocomposite films with antimicrobial, anti-inflammatory, and good mechanical properties to be applied in periodontal pockets. The composite film is eco-friendly synthesized from poly(vinyl alcohol) (PVA) cross-linked with oxidized chitosan (OxCS). Silver nanoparticles (AgNps) were inserted during film synthesis by adding freshly chitosan-capped AgNps colloidal solution to the polymer mixture; the addition of AgNps up to 1.44 wt.% improves the physico-chemical properties of the film. The characterization of the films was performed by FT-IR, atomic mass spectrometry, X-ray spectroscopy, and SEM. The films displayed a high swelling ratio (162%), suitable strength (1.46 MPa), and excellent mucoadhesive properties (0.6 N). Then, ibuprofen (IBF) was incorporated within the best film formulation, and the IBF-loaded PVA/OxCS-Ag films could deliver the drug in a sustained manner up to 72 h. The biocomposite films have good antimicrobial properties against representative pathogens for oral cavities. Moreover, the films are biocompatible, as demonstrated by in vitro tests on HDFa cell lines. Full article

Periodontitis is a dysbiotic biofilm-induced and host-mediated inflammatory disease of tooth supporting tissues that leads to progressive destruction of periodontal ligament and alveolar bone, thereby resulting in gingival recession, deep periodontal pockets, tooth mobility and exfoliation, and aesthetically and functionally compromised dentition. Due to the improved biopharmaceutical and pharmacokinetic properties and targeted and controlled drug release, nano-based drug delivery systems have emerged as a promising strategy for the treatment of periodontal defects, allowing for increased efficacy and safety in controlling local inflammation, establishing a regenerative microenvironment, and regaining bone and attachments. This review provides an overview of nano-based drug delivery systems and illustrates their practical applications, future prospects, and limitations in the field of periodontal tissue regeneration. Full article