Search Results (12)

Due to its numerous advantages, such as excellent drug accessibility, rapid absorption, and bypass of first-pass metabolism, the route of drug administration that involves crossing the oral mucosa is highly favored. As a result, there is significant interest in investigating the permeability of drugs through this region. The purpose of this review is to describe the various ex vivo and in vitro models used to study the permeability of conveyed and non-conveyed drugs through the oral mucosa, with a focus on the most effective models. Currently, there is a growing need for standardized models of this mucosa that can be used for developing new drug delivery systems. Oral Mucosa Equivalents (OMEs) may provide a promising future perspective as they are capable of overcoming limitations present in many existing models. Full article

Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm²/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4–5 cell layers with basal cells still undergoing mitosis. The optimum period at the air–liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca²⁺, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes’ differentiation and inflammatory conditions, etc.). Full article

The hypothalamic–pituitary–thyroid (HPT) axis is crucial in regulating thyroid hormone levels that contribute to the development and homeostasis of the human body. Current literature supports the presence of a local HPT axis equivalent within keratinocytes of the skin, with thyroid hormones playing a potential role in cancer progression. However, this remains to be seen within oral tissue cells. An electronic search of Scopus and PubMed/Medline databases was conducted to identify all original publications that reported data on the production or effects of HPT axis components in normal or malignant cells of the oral cavity. The search identified 221 studies, of which 14 were eligible. Eight studies were retrospective analyses of clinical samples, one study involved both in vivo and in vitro experiments, and the remaining five studies were conducted in vitro using cell lines. The search identified evidence of effects of HPT components on oral cancer cells. However, there were limited data for the production of HPT axis components by oral tissues. We conclude that a possible role of the local HPT axis equivalent in the oral mucosa may not be established at present. The gaps in knowledge identified in this scoping review, particularly regarding the production of HPT components by oral tissues, warrant further investigation. Full article

Although three-dimensional (3D) co-culture of gingival keratinocytes and fibroblasts-populated collagen gel can mimic 3D structure of in vivo tissue, the uncontrolled contraction of collagen gel restricts its application in clinical and experimental practices. We here established a stable 3D gingival tissue equivalent (GTE) using hTERT-immortalized gingival fibroblasts (hGFBs)-populated collagen gel directly crosslinked with genipin/cytochalasin D and seeding hTERT-immortalized gingival keratinocytes (TIGKs) on the upper surface for a 2-week air–liquid interface co-culture. MTT assay was used to measure the cell viability of GTEs. GTE size was monitored following culture period, and the contraction was analyzed. Immunohistochemical assay was used to analyze GTE structure. qRT-PCR was conducted to examine the mRNA expression of keratinocyte-specific genes. Fifty µM genipin (G50) or combination (G + C) of G50 and 100 nM cytochalasin D significantly inhibited GTE contraction. Additionally, a higher cell viability appeared in GTEs crosslinked with G50 or G + C. GTEs crosslinked with genipin/cytochalasin D showed a distinct multilayered stratified epithelium that expressed keratinocyte-specific genes similar to native gingiva. Collagen directly crosslinked with G50 or G + C significantly reduced GTE contraction without damaging the epithelium. In summary, the TIGKs and hGFBs can successfully form organotypic multilayered cultures, which can be a valuable tool in the research regarding periodontal disease as well as oral mucosa disease. We conclude that genipin is a promising crosslinker with the ability to reduce collagen contraction while maintaining normal cell function in collagen-based oral tissue engineering. Full article

Oral mucosa is used in various surgical fields as a graft for the reconstruction of tissue defects. Tissue engineering of oral mucosa equivalents using autologous cells represents a suitable less burdensome alternative. The survival of the multilayered epithelium is essential for the functionality of the tissues in vivo. To ensure its functionality after transplantation, mucosa equivalents in vitro were subjected to extracorporeal shock wave therapy (ESWT) to determine whether this treatment stimulated the formation and differentiation of the epithelium. Mucosa equivalents treated with ESWT were examined for cellular metabolic activity using AlamarBlue^TM assay. The formation of vascular structures, basement membrane, and multilayered epithelium were examined using confocal fluorescence microscopy and immunohistochemistry. The potential ingrowth in vivo was simulated using the chorioallantoic membrane model (CAM assay) in ovo. ESWT on culture day 19 of oral mucosa equivalents resulted in slightly increased cellular metabolic activity. The in vitro development of basement membrane and multilayer epithelium was stimulated by ESWT. Additionally, in the CAM assay, ESWT led to a more pronounced multilayered epithelium. Thus, ESWT stimulated the formation of a more distinct and differentiated multilayered epithelium of oral mucosa equivalents in vitro and might increase the chance of efficient ingrowth, survival, and functionality of tissue equivalents in vivo. Full article

Neuropeptides have been known for over 50 years as chemical signals in the brain. However, it is now well established that the synthesis of this class of peptides is not restricted to neurons. For example, human skin not only expresses several functional receptors for neuropeptides but, also, can serve as a local source of neuroactive molecules such as corticotropin-releasing hormone, melanocortins, and β-endorphin. In contrast, an equivalent of the hypothalamic-pituitary axis in the oral mucosa has not been well characterized to date. In view of the differences in the morphology and function of oral mucosal and skin cells, in this review I surveyed the existing evidence for a local synthesis of hypothalamic-pituitary, opiate, neurohypophyseal, and neuroendocrine neuropeptides in both epidermal and oral keratinocytes. Full article

This study was conducted to investigate the therapeutic effect of hydro-alcoholic extract of Spirulina platensis (SP), golden kiwifruit (Actinidia chinensis) flesh (KF), and golden kiwifruit peel (KP) individually or in combination (SFP) on indomethacin-induced gastric ulcer in rats. Negative control rats (GI) were orally administered distilled water in parallel with other treatments. The positive control rat group (GII) was administered 30 mg kg⁻¹ indomethacin to induce gastric ulcers. The KF and KF extracts were used individually or together with SP in treating indomethacin-induced gastric ulcerated rat groups. Gastric ulcerated rat’s groups GIII, GIV, GV, GVI, and GVII were orally administered at 30 mg kg⁻¹ rat body weight as total phenolic content (TPC) equivalent from SP, KF, KP, SPF extracts, and Lansoprazole (30 mg kg⁻¹, as reference drug) daily up to 14 days, respectively. The relevant biochemical parameters, antioxidant biomarkers, and histopathological examination were examined. Remarkably, treating rats with SP, KF, KP, and SFP extracts markedly reduced gastric juice and stomach volume expansion induced by indomethacin. The SP significantly retrieved the pH of gastric juice to a regular rate compared to GI. The ulcer index (UI) was significantly attenuated by SP, KF, KP, and SFP administration. The protection index percentage (PI %) was 80.79, 54.51, 66.08, 75.74, and 74.86% in GIII, GIV, GV, GVI, and GVII, respectively. The gastric mucin content was significantly better attenuated by 95.7 in GIII compared to its content in GI. Lansoprazole increased mucin content by 80.3%, which was considerably lower than SP and SFP. SP, KF, KP, SFP, and Lansoprazole improved the reform of gastric mucosal-increased secreted mucus by 95.6, 61.3, 64.8, 103.1, and 80.2% in GIII, GIV, GV, GVI, and GVII, respectively. Interestingly, SFP efficiently increased vit. B₁₂ level by 46.0% compared to other treatments. While Lansoprazole administrating did not significantly attenuate vit. B₁₂ level. The SP and SFP improved iron and Hemoglobin (HB) levels depending on treatment. SP, KF, KP, and SFP significantly decreased the malondialdehyde (MDA) and increased reduced glutathione (GSH) as well as superoxide dismutase (SOD) levels in blood and stomach tissues. The most potent effect was observed with SP, and SFP was even better than Lansoprazole. Histopathologically, treating rats with SP extract showed a marked reduction of gastric damage and severity changes induced by indomethacin. KP was much better than KF in lessening gastric histopathological damages caused by indomethacin. SFP significantly alleviates gastric histopathological alterations. The lansoprazole-treated group (GVII) greatly relieved the gastric histopathological changes and recorded mild focal necrosis and desquamation of the mucosa in addition to mild oedema in the serosal layer. In conclusion, the presented results proved the antiulcer potential of SP and A. chinensis extracts against an indomethacin-induced gastric ulcer in rats, which may be due to their antioxidant and anti-inflammation efficiency. Thus, these data suggested that SP, KF, KP, and SFP extracts as natural and safe alternatives have a gastroprotective potential against indomethacin-induced gastric ulceration. The antioxidative and anti-inflammatory properties are probable mechanisms. Full article

Three-dimensional (3D) printing technology allows the production of an individualized 3D object based on a material of choice, a specific computer-aided design and precise manufacturing. Developments in digital technology, smart biomaterials and advanced cell culturing, combined with 3D printing, provide promising grounds for patient-tailored treatments. In dentistry, the “digital workflow” comprising intraoral scanning for data acquisition, object design and 3D printing, is already in use for manufacturing of surgical guides, dental models and reconstructions. 3D printing, however, remains un-investigated for oral mucosa/gingiva. This scoping literature review provides an overview of the 3D printing technology and its applications in regenerative medicine to then describe 3D printing in dentistry for the production of surgical guides, educational models and the biological reconstructions of periodontal tissues from laboratory to a clinical case. The biomaterials suitable for oral soft tissues printing are outlined. The current treatments and their limitations for oral soft tissue regeneration are presented, including “off the shelf” products and the blood concentrate (PRF). Finally, tissue engineered gingival equivalents are described as the basis for future 3D-printed oral soft tissue constructs. The existing knowledge exploring different approaches could be applied to produce patient-tailored 3D-printed oral soft tissue graft with an appropriate inner architecture and outer shape, leading to a functional as well as aesthetically satisfying outcome. Full article

Background: Cone beam computed tomography (CBCT) is often used in different fields of dental science, especially in complex anatomical districts like the endodontic one. The aim of this study is to propose a low-dose CBCT protocol useful in cases of endodontic lesions. Methods: The device used was a MyRay Hyperion X9-11x5; the low dose setting of the machine was 90 Kv, 27 mAs, CTDI/Vol 2.89 mGy. The absorbed organ doses have been evaluated with an anthropomorphic phantom loaded with thermoluminescent dosimeters positioned at the level of sensitive organs like brain, bone marrow, salivary glands, thyroid, esophagus, oral mucosa, extrathoracic airways, and lymph nodes. Equivalent and effective doses have been calculated; the last one has been calculated using the recommendations approved by the Main Commission of ICRP (International Commission Radiological Protection) in March 2007. For the assessment of image quality, five senior clinicians, independent and experienced clinicians, were asked to state if CBCT scans were accurate enough to assess endodontic lesions. Results: The use of a low-dose CBCT acquisition produced the lowest organ dose (5.01 microSv) at the level of the esophagus. Image quality has been considered accurate enough for endodontic diagnostic needs. Conclusions: CBCT low-dose protocol can be used over the standard one in endodontic special cases because it provides a significantly lower radiation dose to the patients while ensuring good image quality. However, further studies are necessary to evaluate the opportunity of low-dose CBCT exams in endodontic clinical practice. Full article

The absorption study of drugs through different biological membranes constitutes an essential step in the development of new pharmaceutical dosage forms. Concerning orally administered forms, methods based on monolayer cell culture of Caco-2 (Caucasian colon adenocarcinoma) have been developed to emulate intestinal mucosa in permeability studies. Although it is widely accepted, it has disadvantages, such as high costs or high technical complexity, and limitations related to the simplified structure of the monolayer or the class of molecules that can be permeated according to the transport mechanisms. The aim of this work was to develop a new ex vivo methodology which allows the evaluation of the intestinal apparent permeability coefficient (P_app) while using fewer resources and to assess the correlation with Caco-2. To this end, pig (Sus scrofa) duodenum segments were mounted in Franz diffusion cells and used to permeate four different drugs: ketorolac tromethamine (Kt), melatonin (Mel), hydrochlorothiazide (Htz), and furosemide (Fur). No statistically significant differences (p > 0.05) were observed corelating P_app values from Franz diffusion cells and Caco-2 cell experiments for Kt, Htz, and Fur. However, there were statistically significant differences (p < 0.05) correlating P_app values and Mel. The difference is explained by the role of Mel in the duodenal epithelial paracellular permeability reduction. Ex vivo permeation may be an equivalent method to Caco-2 for drugs that do not produce intestinal membrane phenomena that could affect absorption. Full article

Background: Celiac disease (CD) is an immunologically-mediated disorder characterized by duodenal mucosa villi atrophy. Iron absorption is usually reduced in celiac patients making every kind of oral iron treatment unhelpful because of malasorption. Feralgine™ is a new product that has been demonstrated to be more bioavailable. As such, the aim of our study was to evaluate the absorption of Feralgine™ in adult patients with CD. Methods: Twenty-six adults affected by Iron Deficiency Anemia (IDA), of which 14 were also affected by CD and 12 were not affected by CD, were enrolled. An oral iron absorption test (OIAT) was performed in each patient by administrating Feralgine™, and serum iron was evaluated at baseline (T0) and after 2 h (T1) from the oral iron ingestion. Results: The OIAT was well tolerated in all patients, and, surprisingly, an equivalent statistically significant improvement in serum iron occurred in the two groups of patients (IDA plus CD: T0 = 28.21 µg/dL vs. T1 = 94.14 µg/dL p = 0.004 and IDA without CD: T0 = 34.91 µg/dL vs. T1 = 118.83 µg/dL, p = 0.0003). Conclusions: These results demonstrated the high absorption of Feralgine™ in celiac patients, confirming our previous data obtained with Ferrous Bysglicinate in children with CD. Full article

The administration of biological compounds that optimize health benefits is an ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological compounds have been administered via many different routes in order to produce a systemic pharmacological effect. The article summarizes the findings from an Australian comparative study in adults administered vitamin B₁₂ through different oral delivery platforms. A total of 16 subjects (9 males, 7 females) voluntarily partook in a comparative clinical study of five different vitamin B₁₂ formulations across a six-month period, completing 474 person-hours of cumulative contribution, that was equivalent to an n = 60 participation. A nanoparticle delivered vitamin B₁₂ through a NanoCelle platform was observed to be significantly (p < 0.05) better absorbed than all other dose equivalent platforms (i.e., tablets, emulsions, or liposomes) from baseline to 1, 3, and 6 h of the study period. The nanoparticle platform delivered vitamin B₁₂ demonstrated an enhanced and significant absorption profile as exemplified by rapid systemic detection (i.e., 1 h from baseline) when administered to the oro-buccal mucosa with no reports of any adverse events of toxicity. The nanoparticle formulation of methylcobalamin (1000 µg/dose in 0.3 mL volume) showed bioequivalence only with a chewable-dissolvable tablet that administered a five times higher dose of methylcobalamin (5000 µg) per tablet. This study has demonstrated that an active metabolite embedded in a functional biomaterial (NanoCelle) may constitute a drug delivery method that can better access the circulatory system. Full article