Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.

Donepezil nasal delivery strategies are being continuously investigated for advancing therapy in Alzheimer’s disease. The aim of this study was to develop a chitosan-based, donepezil-loaded thermogelling formulation tailored to meet all the requirements for efficient nose-to-brain delivery. A statistical design of the experiments was implemented for the optimisation of the formulation and/or administration parameters, with regard to formulation viscosity, gelling and spray properties, as well as its targeted nasal deposition within the 3D-printed nasal cavity model. The optimised formulation was further characterised in terms of stability, in vitro release, in vitro biocompatibility and permeability (using Calu-3 cells), ex vivo mucoadhesion (using porcine nasal mucosa), and in vivo irritability (using slug mucosal irritation assay). The applied research design resulted in the development of a sprayable donepezil delivery platform characterised by instant gelation at 34 °C and olfactory deposition reaching a remarkably high 71.8% of the applied dose. The optimised formulation showed prolonged drug release (t_1/2 about 90 min), mucoadhesive behaviour, and reversible permeation enhancement, with a 20-fold increase in adhesion and a 1.5-fold increase in the apparent permeability coefficient in relation to the corresponding donepezil solution. The slug mucosal irritation assay demonstrated an acceptable irritability profile, indicating its potential for safe nasal delivery. It can be concluded that the developed thermogelling formulation showed great promise as an efficient donepezil brain-targeted delivery system. Furthermore, the formulation is worth investigating in vivo for final feasibility confirmation.

Objectives: The study aimed to determine the relationship between the mandibular asymmetry index according to Kjellberg between patients with painful unilateral anterior disc displacement (DD) and asymptomatic volunteers without disc displacement. Vertical measurements were performed on a panoramic single-image radiograph, and the disc status was confirmed by magnetic resonance imag-ing (MRI). Material and methods: Two groups of subjects were retrospectively selected, 40 patients (the overall mean age was 35.5 years; 75% female) with temporomandibular disorder symptoms con-firmed by RDC/TMD axis I and manual functional analysis. Unilateral DD was determined by MRI. A comparative group of asymptomatic volunteers (20 dental students with a mean age of 23.4 years; 72% female) had the physiological position of the disc determined by MRI. The vertical asymmetry of the condyle was determined by the method of Kjellberg et al. The symmetry of the gonial angle of the mandible was also measured. Results: A comparison of the mean of the asymmetry index between patients (average 90.89 & PLUSMN;7.08%) and asymptomatic volunteers (mean 95.86 & PLUSMN;4.44%) showed a statis-tically significant difference (p=0.0029). There was no difference (p=0.088) in gonial angle symme-try between the patients (mean 96.48 & PLUSMN;2.96 & DEG;) and the asymptomatic volunteers (mean 97.52 & PLUSMN;2.31 & DEG;). The distribution of the presence of individual DD diagnoses (partial and total displacement with re-duction, displacement without reduction) in patients diagnosed with asymmetry of the mandible was without statistical significance (p>0.05). Conclusion: This study actually points to the asymmetry of the mandible as a potential morphological risk of anterior DD.

Orthopantomography is amongst the most commonly used dental imaging modalities. Calcifications in the projection of carotids on orthopantomographs are found in 3-15% of general population and commonly represent calcified atherosclerotic plaques. Carotid atherosclerotic changes are one of the most frequent causes of stroke, which is the second most common cause of death and the leading cause of disability globally. Our aim was to determine the relationship between calcifications in the projection of carotids on orthopantomographs, carotid stenosis and stroke, and the correlation between stroke risk factors, calcifications on orthopantomographs and the degree of carotid stenosis. Doppler ultrasound and brain MRI were performed in 41 patients with unilateral or bilateral calcifications on orthopantomographs. Anamnestic data relevant to stroke risk were gathered. Significant stenosis >50% was found in almost 15% of our patients. There was a significant correlation between hypertension and carotid calcifications. No statistically significant correlation between calcifications and significant stenosis was found. Patients with previous stroke were approximiately 5 years older than those without stroke. Preliminary results show no statistically significant correlation between calcifications on orthopantomography and significant carotid stenosis, but further investigation is needed.

The aim of the study was to examine the prevalence of head injuries, acute stroke and brain tumors obtained from computed tomography (CT) scans in the emergency department (ED) during a one-year period. We also assessed the potential...

Osteoarthritis (OA) of the temporomandibular joint (TMJ) is a degenerative condition affecting both osseous and soft tissue structures. Cone beam computed tomography (CBCT) offers detailed visualization of osseous changes, while magnetic resonance imaging (MRI) provides superior assessment of soft tissues, particularly the articular disc. The relationship between bony degeneration and disc abnormalities remains poorly defined. This study examined the correlation between CBCT-identified osseous radiological features of TMJ OA and MRI-detected disc displacement patterns. A cross-sectional analysis was performed on 198 TMJs from 99 patients clinically diagnosed with TMJ OA, where both MRI and CBCT imaging were performed in the same patient to enable direct comparative analysis. MRI was used to classify disc position as normal, partial displacement with reduction, complete displacement with reduction (DDR), or complete displacement without reduction (DDWR). CBCT scans were assessed for degenerative bone changes, including subchondral cysts, erosions, generalized sclerosis, osteophytes, and loose calcified bodies. OA severity was graded using the Ahmad and Schiffman criteria. Statistical evaluation was conducted using Fisher’s Exact Test. A statistically significant correlation was found between OA severity and disc displacement type (p < 0.001). DDWR was most frequently associated with Grade 2 OA (26.8%). Subchondral cysts (p = 0.004), erosions (p < 0.001), generalized sclerosis (p < 0.001), and osteophytes (p < 0.001) occurred with significantly higher prevalence in patients presenting with DDWR. Loose calcified bodies showed no significant association with disc position (p = 0.191). There is an association between degenerative osseous changes and disc displacement patterns in TMJ OA, and DDWR represents a more advanced stage of internal derangement accompanied by pronounced bone remodeling. These results support the combined use of CBCT and MRI for the comprehensive assessment of TMJ OA.