Elena Dinte

Oral inflammatory diseases and oral cancer are multifactorial pathologies that share common underlying mechanisms, including oral dysbiosis, chronic inflammation and alterations of the immune response. Macrophage polarization represents the key link between these conditions, with crucial implications in disease progression and therapeutic outcome. In periodontitis, overactive M1 pro-inflammatory macrophages maintain persistent inflammation leading to periodontal tissue breakdown, whereas the M2-like cells are anti-inflammatory and facilitate inflammation resolution and tissue healing. Conversely, in oral squamous cell carcinoma, dominant M2-like tumor associated macrophages suppress anti-cancer immunity and promote aggressive tumor progression, metastasis and recurrence. These contrasting roles of macrophages highlight the importance of novel therapeutic approaches aiming at disease-dependent modulation of macrophage polarization. The therapeutic application of nanovehicles loaded with macrophage-polarizing agents offers significant benefits due to their capacity to overcome the barriers imposed by the specific anatomical characteristics of the oral cavity, while optimizing the pharmacokinetic and stability parameters of therapeutic agents that modulate M1/M2 activation pathways. Functionalizing nanosystems with moieties responsive to the pathological microenvironment—or capable of active molecular targeting—combined with mucoadhesive application or intra-tumoral injection, ensures increased bioavailability of active molecules. This targeted approach maximizes therapeutic efficacy while avoiding exposure of healthy tissues. Optimizing formulation technologies to yield nanosystems tailored to the specific features of a pathology and to immunomodulatory strategies can provide high-efficiency, sustained-release platforms for restoring the physiological parameters of oral tissues. This narrative review summarizes the implication of macrophage phenotypes in periodontitis and oral squamous cell carcinoma and discusses novel nanodelivery systems as immunomodulatory therapeutic approaches.

The study aimed to develop a mucoadhesive thermosensitive buccal gel capable of forming an artificial clot after application in the extraction socket and providing prolonged release for metronidazole (MZ) and ibuprofen (IB). The critical quality attributes of the product were systematically evaluated using Ishikawa (cause–effect) diagrams as a risk assessment tool, considering the factors related to the formulation, process, and methodology. Subsequently, Failure Mode and Effects Analysis (FMEA) was used to identify the critical parameters of the formulation and process characterized by a high probability of occurrence and a significant impact on product performance. The influence of qualitative and quantitative formulation variables was further investigated using two experimental designs, applied for both screening and optimization purposes. The rheological, adhesion, and in vitro release properties of the drugs were studied, and the optimized formulation for these characteristics contains Poloxamer 407 20.99% and HPMC K100M:K4M 1:1, 0.74%. The release of MZ and IB was prolonged over 8 h and followed Peppas’s kinetics. The optimized formula had an appropriate pH and an acceptable ex vivo mucoadhesion time. Stability studies revealed the preservation of mechanical properties and a recovery coefficient for MZ and IB of over 90%, after 12 months of storage. The optimized formula may be a potential candidate for the prevention of alveolar osteitis.

Background: Mechanical subgingival instrumentation remains the gold standard in periodontitis treatment; however, it may leave residual debris and induce surface alterations. Adjunctive strategies such as air polishing and ethylenediaminetetraacetic acid (EDTA) might optimize root surface conditions. Objective: To evaluate, by scanning electron microscopy (SEM), the effects of scaling and root planing (SRP) combined with EDTA, with or without adjunctive erythritol- or glycine-based air polishing, on root surface alterations and smear layer formation. Materials and Methods: Ten extracted human teeth affected by periodontitis (yielding twenty samples) were included. Two teeth served as descriptive controls. The remaining teeth were allocated to four treatment groups. The first three groups included samples obtained from the middle portion of the roots: S (SRP + EDTA), Se (SRP + erythritol air polishing + EDTA), and Sg (SRP + glycine air polishing + EDTA). The fourth group, Js, consisted of samples from the cementoenamel junction (CEJ) treated with SRP + EDTA. SEM images were appreciated qualitatively and assessed using ordinal scores (0–3) for marks, cracks (×100), and smear layer (×1000). Non-parametric statistics were applied. Results: A significant difference in mark scores was found among S, Se, and Sg samples (H = 13.411, p = 0.001), with Se samples showing lower mark scores than S (p = 0.001). Crack scores also differed among groups (H = 12.038, p = 0.002), with higher values observed in Se compared to S (p = 0.001). Smear layer scores did not differ among groups (H = 0.102, p = 0.950). Compared with S samples, Js differed only in marks (p = 0.009), with no significant differences in cracks or smear layer. Conclusions: Within the limitations of this in vitro study, root surface alterations and smear layer formation showed variable responses across treatment protocols, with comparable smear layer scores. Similar effects were observed for CEJ and mid-root samples; however, these findings should be interpreted with caution. Further studies are needed to clarify the potential clinical relevance of these observations.

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.

Enhancement of orthodontic tooth movement (OTM) through local administration of biofunctional molecules has become increasingly significant, particularly for adult patients seeking esthetic and functional improvements. This comprehensive systematic review analyzes the efficacy of various biofunctional molecules in modulating OTM, focusing on the method of administration and its feasibility, especially considering the potential for topical application. A search across multiple databases yielded 36 original articles of experimental human and animal OTM models, which examined biofunctional molecules capable of interfering with the biochemical reactions that cause tooth movement during orthodontic therapy, accelerating the OTM rate through their influence on bone metabolism (Calcitriol, Prostaglandins, Recombinant human Relaxin, RANKL and RANKL expression plasmid, growth factors, PTH, osteocalcin, vitamin C and E, biocompatible reduced graphene oxide, exogenous thyroxine, sclerostin protein, a specific EP4 agonist (ONO-AE1-329), carrageenan, and herbal extracts). The results indicated a variable efficacy in accelerating OTM, with Calcitriol, Prostaglandins (PGE1 and PGE2), RANKL, growth factors, and PTH, among others, showing promising outcomes. PGE1, PGE2, and Calcitriol experiments had statistically significant outcomes in both human and animal studies and, while other molecules underwent only animal testing, they could be validated in the future for human use. Notably, only one of the animal studies explored topical administration, which also suggests a future research direction. This review concluded that while certain biofunctional molecules demonstrated potential for OTM enhancement, the evidence is not definitive. The development of suitable topical formulations for human use could offer a patient-friendly alternative to injections, emphasizing comfort and cost-effectiveness. Future research should focus on overcoming current methodological limitations and advancing translational research to confirm these biomolecules’ efficacy and safety in clinical orthodontic practice.

Enhancement of orthodontic tooth movement (OTM) through local administration of biofunctional molecules has become increasingly significant, particularly for adult patients seeking aesthetic and functional improvements. This comprehensive systematic review analyzes the efficacy of various biofunctional molecules in modulating OTM, focusing on the method of administration and its feasibility, especially considering the potential for topical application. A search across multiple databases yielded 36 original articles of experimental human and animal OTM models, which examined biofunctional molecules capable of interfering with the biochemical reactions that cause tooth movement during orthodontic therapy, accelerating the OTM rate through their influence on the bone metabolism (Calcitriol, Prostaglandins, Recombinant human Relaxin, RANKL and RANKL expression plasmid, growth factors, PTH, osteocalcin, vitamin C and E, biocompatible reduced graphene oxide, exogenous thyroxine, sclerostin protein, a specific EP4 agonist (ONO-AE1-329), carrageenan and herbal extracts). The results indicated a variable efficacy in accelerating OTM, with Calcitriol, Prostaglandins (PGE1 and PGE2), RANKL, growth factors and PTH, among others, showing promising outcomes. PGE1, PGE2 and Calcitriol experiments had statistically significant outcomes in both human and animal studies, and, while other molecules underwent only animal testing, they could be validated in the future for human use. Notably, only one of the animal studies explored topical administration, which also suggests a future research direction. This review concluded that while certain biofunctional molecules demonstrated potential for OTM enhancement, the evidence is not definitive. The development of suitable topical formulations for human use could offer a patient-friendly alternative to injections, emphasizing comfort and cost-effectiveness. Future research should focus on overcoming current methodological limitations and advancing translational research to confirm these biomolecules' efficacy and safety in clinical orthodontic practice.

The topical administration of medicines is the preferred route in ocular therapy, at least for the anterior segment of the eye. However, the eye’s inherent functional and biological barriers all work against the active pharmaceutical ingredient (API) to efficiently reach the targeted retinal structures. The main objective of this article is to offer a systematic review of the scientific literature in recent years, focusing on the latest developments of topical treatment intended for retinal degenerative diseases. Database search returned 102 clinical studies, focused on topical treatment for age macular degeneration, macular edemas (in diabetic retinopathy, surgery related or in retinal dystrophies) or glaucoma. After the exclusion of low-powered studies and those combining vitreo-retinal surgery, 35 articles remained for analysis. Currently, the topical treatment of retinal degenerative diseases is limited by the difficulty to deliver effective drug concentrations to the posterior eye structures. However, in the case of drug classes like NSAIDs, the presence of certain molecular and metabolic features for specific representatives makes the topical administration currently feasible in several clinical contexts. For other drug classes, either a fine-tuning of the API’s pharmacokinetic profile or the use of more advanced formulation strategies, such as rationally designed nanostructured drugs and vehicles, crystalline polymorphs or supramolecular complexes, could bring the much awaited breakthrough for a more predictable and controlled delivery towards the retinal structures and could eventually be employed in the future for the development of more effective ways of delivering drugs to the posterior eye, with the ultimate goal of improving their clinical efficacy.

The goal of our study was to find an easy and suitable skin burn model for rabbits, to identify the temperature and contact time to reach a deep 2nd degree burn, and to find the best wound dressing fixation method. We used New Zealand male rabbits as experimental models. On a pilot study, with a copper device heated to temperatures between 43-48 Celsius degrees, the burn was inflicted using contact timesof 3, 4, 5, and 7 seconds. The burn depth was evaluated histological. Twenty-four rabbits were used to evaluate four dressing fixation methods: regular dressing with retention bandages; skin stapler; collars and body resin cast. A 2nd degree deep burn was obtained at 43 degrees for 4 seconds. The retention elastic bandages were removed within hours and the skin staplers were removed with teeth leaving wounds on the skin. The collars were more successful but produced superficial neck lesions. The body resin casts were the most successful. The best contention method was the bpdy resin cast.

The possibility to use poly(ethylene oxide) as a polymeric matrix for some pharmaceutical products was analyzed. The behavior of the polymer in the aqueous solutions and the possible interactions between the polymer and the clotrimazole were investigated by Raman spectroscopy. Repeated action of the water on the polymeric conformation is a reversible process and the introduction of the clotrimazole in the polymeric gel do not modify the properties of the active substance of the pharmaceutical product.

This study presents the toxic effects of a very known and used compound in pharmaceutical products and from cosmetic market, a detergent (surface-active) anionic. The presented data underlined the effects of an ointment base with sodium lauryl sulfate, with various concentrations of this detergent, respectively: 0.5%, 1% and 3%, in a long term utilization of this, on an animal model with Sprague Dawley rats.