Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus.

Chronic and allergic rhinosinusitis impacts approximately 12% of the global population. Challenges in rhinosinusitis treatment include paranasal sinus inaccessibility and variability in delivery efficiency among individuals. This study addresses these challenges of drug delivery by developing a high-efficiency, low-variability protocol for nasal drop delivery to the ostiomeatal complex (OMC) and maxillary sinus. Patient-specific nasal casts were dissected to reveal the configurations of conchae and meatus, providing insights into anatomical features amendable for sinus delivery. Fluorescent dye-enhanced videos visualized the dynamic liquid translocation in transparent nasal casts, allowing real-time assessment and quick adjustment to delivery parameters. Dosimetry to the OMC and maxillary sinus were quantified as drop count and mass using a precision scale. Key delivery factors, including the device type, formulation, and head-chin orientation, were systematically investigated in a cohort of ten nasal casts. Results show that both the squeeze bottle and soft-mist nasal pump yielded notably low doses to the OMC with high variability, and no dose from these two devices was detected within the maxillary sinuses. In contrast, the proposed approach, which included a curved nozzle surpassing the nasal valve and leveraged gravity-driven liquid translocation along the lateral nasal wall, delivered significant doses to the OMC and maxillary sinus. Iterative experimentations identified the optimal head tilt to be 40° and chin tilt to be° from the lateral recumbent position. Statistical analyses established the drop count required for effective OMC/sinus delivery. The proposed delivery protocol holds the potential to enhance chronic rhinosinusitis treatment outcomes with low variability. The dual role of nasal anatomy in posing challenges and offering opportunities highlights the need for future investigations using diverse formulations in a larger cohort of nasal models. Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus.

Targeted drug delivery to the inferior meatus cavity of the nasal airway using a nasal spray device with angled tip.

BACKGROUND AND OBJECTIVE: Nowadays, by advancement in computational tools, Computational Fluid and Particle Dynamics (CFPD) technique can be used more than ever. The main aim of this study is using a nasal spray device with angled tip to deliver drug particles to the inferior meatus cavity for treatment purposes. In the present study, the drug delivery to the lower regions of the nasal cavity will be improved that has been considered less in the literature. METHODS: For this purpose, a spray with an angled tip was used, and the deposition of sprayed particles was compared with a spray with a straight tip. Based on the objectives presented above, a realistic model of the nasal route, including facial geometry, and paranasal sinuses obtained from a series of Computed tomography (CT) scan images, as well as the geometry of a nasal spray with two types of tip were developed. RESULTS: It is observed that by using the spray with the straight tip, particles were mainly deposited in the middle and superior regions of the nasal cavity and no particles entered the inferior meatus airway. The results proved that the spray with the angled tip improved the regional deposition percentage in the inferior meatus cavity up to 2.4% of the total sprayed particles and 1 mg drug mass delivered to this region. The majority of these particles had a diameter between 15-55 µm and that could be considered by spray designers to produce more compatible sprays with the targeted region. Also, most particles were deposited near the inferior meatus cavity and so there is a strong chance to be absorbed and delivered to this region. CONCLUSION: The deposition pattern and particle size contour due to the spray with the angled tip can give sight to the designers and producers of nasal sprays to build more efficient types for better targeted drug delivery purposes. With this spray type, deposited particles were observed in the inferior meatus that never happened with the straight type. Also, the angled tip of the nasal spray shows the benefit of the ease of use for the user.

A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.

RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer's disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer's disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).