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The field of nasal drug delivery gained enormously on interest over the past decade. Performing nasal in vivo studies is expensive and time-consuming, but also unfeasible for an initial high-throughput compound and formulation screening. Therefore, the development of fast and high-throughput in vitro models to screen compounds for their permeability through the nasal epithelium and mucosa is constantly expanding. Yet, the protocols used for nasal in vitro permeability studies are varying, which limits the comparability and reproducibility of generated data. This project aimed to elucidate the influence of different culture and assay parameters of RPMI 2650 cells grown under air–liquid interface (ALI) conditions on the transepithelial electrical resistance (TEER) and apparent permeability (Papp) values of five selected reference compounds, covering the range of low to moderate to high permeability. The influence of the passage number, seeding density, and timepoint of airlift was minimal in our approach, while the substrate pore density had a significant influence on the Papp values of carbamazepine, propranolol, and metoprolol, classified as highly permeable compounds, but not on atenolol and aciclovir. Elevation of the experimental concentration of carbamazepine, propranolol, and metoprolol in the donor compartment had an increasing effect on the Papp values, while prolonging the assay time did not have a significant influence. Based on the results reported here, RPMI 2650 cells cultured under ALI conditions offer the possibility of a standardized high-throughput screening model for small molecules and their formulations for in vitro drug permeation studies to predict and select optimal conditions for their nasal delivery. [ABSTRACT FROM AUTHOR]

Background. Rhinomanometry is an objective way of assessing nasal patency. Due to advances in technology and the use of microcomputers connected to measuring instruments, the use of this approach has increased. Rhinomanometry evaluates nasal resistance by measuring airflow and transnasal pressure gradient. With the help of this examination, the presence of a nasal respiratory obstruction is detected, and it is evaluated which nosological structure continuously causes it, in this case the hypertrophy of the inferior nasal turbinates. The purpose of the research is to evaluate the effectiveness of the functional examination such as the anterior rhinomanometry in monitoring the results of laser surgical treatment in children with chronic hypertrophic rhinitis. Materials and methods. The given study was carried out in the pediatric otorhinolaryngology clinic of the Emilian Coţaga Republican Children’s Clinical Hospital. The research involved a group of 120 children with hypertrophic chronic rhinitis, aged between 8–17 years, divided into three groups of 40 children each, treated surgically by 3 techniques: group 1 — cauterization of the inferior nasal turbinates with bipolar forceps, group 2 — shaver mucotomy and group 3 — diode laser surgery. In all patients, rhinomanometry was performed as an objective preoperative and postoperative examination on the 7th day, after one month, one year and in 12 months. Results. The analysis of the functional examination results demonstrates that the surgical interventions had a beneficial effect in terms of the recovery of the space parameters of the nasal cavities. A more pronounced improvement of the endonasal architectural indices is determined in group 3 where the diode laser surgical technique was used compared to group 2 — only shaver mucotomy and group 1 where the standard surgical technique of cauterization with bipolar forceps was practiced. Conclusions. The functional rhinomanometric results were statistically different after the surgical treatment in all study groups that indicates an important diagnostic value of this examination in the monitoring of postoperative dynamics.

[Display omitted] In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay (PAMPA), a high throughput screening tool, has been applied to evaluate drug permeability across several barriers such as the skin or blood–brain barrier. Herein, a new nasal-PAMPA model was optimized to predict nasal permeability, using a biorelevant donor medium containing mucin. The apparent permeability (P app) of 15 reference compounds was assessed in six different experimental conditions, and the most discriminating and predictive model was applied to a test drug (piroxicam) and mucoadhesive powder formulations loading the same drug. The model with 0.5% (w/v) mucin in the donor compartment and 2% (w/v) phosphatidylcholine in the lipid membrane accurately distinguished high and low permeable compounds. Additionally, it exhibited the highest correlation with permeation across human nasal epithelial cells, RPMI 2650 (R2 = 0.93). When applied to powder formulations, this model was sensitive to the presence of mucoadhesive excipients and the drug solid state. Overall, the nasal-PAMPA model was more rapid than cell-based assays, without requiring specialized training or equipment, showing to be a promising in vitro tool that can be applied in drug and formulation screening for nasal delivery. [ABSTRACT FROM AUTHOR]

Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico⁻chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

Abstract: The nasal pathway represents a non-invasive route for delivery of drugs to the systemic circulation. Nanonization of poorly soluble drugs offers a possibility to increase dissolution properties, epithelial permeability or even bioavailability. The aim of the present study was to use in vitro methods to screen formulations which were intended for nasal application, and to perform animal experiments for recognizing the differences in plasmakinetics of intranasal- and oral-administered meloxicam nanoparticles. Due to nanonization the solubility of meloxicam elevated up to 1.2mg/mL, additionally the extent of dissolution also increased, complete dissolution was observed in 15min. Favorable in vitro diffusion profile of meloxicam nanoparticles was observed and their epithelial permeability through human RPMI2650 cells was elevated. The pharmacokinetic parameters were significantly increased when meloxicam was administered as nanoparticles to rats either nasally (increase of C max 2.7-fold, AUC 1.5-fold) or orally (increase of C max 2.4-fold, AUC 2-fold) as compared to physical mixture of the drug and the excipients. [Copyright &y& Elsevier]

Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico–chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors. [ABSTRACT FROM AUTHOR]

Background. The aim of the study was to determine the efficiency of acoustic rhinometry (AR) in evaluation of nasal permeability in children with chronic and recurrent rhinosinusitis subjected to the surgical treatment. Our work is based on comparative study of nasal permeability after surgical treatment of 215 children with chronic rhinosinusitis. The age of the children was 5-15 years old, 140 boys (65%) and 75 girls (35%). Methods. In conformity with the method of the treatment all patients (215 children) were divided in 2 groups. In the patients from group I (84 children) the standard endoscopic sinus surgery was performed. In the patients from group II (115 children) the minimally invasive endoscopic sinus surgery was performed. 30 healthy children were as a control group. Nasal permeability was estimated by means of acoustic rhinometry. We have estimated the volume of the nasal cavity V (0-5 cm) and the Minimal Cross-sectional Area (MCA) before the treatment, on the 3rd, 24th, and the 36th week after surgical treatment. Results. In healthy children the value of volume of nasal cavity was 5.6±0.28 cm3 in right side and 6.9±0.16 cm3 on the left side, in children with rhinosinusitis the value of volume was statistically significant decreased: 2.75 ±0.22 cm3 in the right side and 3.15±0.20 cm3 on the left side. In healthy children the values of MCA1 and MCA2 estimated before decongestion were 0.59±0.32 cm2 and 0.82±0.17 cm2. In patients from group I before surgical intervention the value of MCA1 was 0.34 ±0.16 cm2,and MCA2 was 0.54±0.14 cm2. In patients from group II we determined MCA1=0.36±0.21 cm2 and MCA2=0.50±0.12 cm2 respectively. On the 3rd week, we attested an increase of V and MCA values in both groups, with a more significant increase in patients from group II. In the 36th week after the treatment, in patients of the study groups, the investigational indices approached, by their value, the results attested in the control group with better results in group II. Conclusion. 1. In children with rhinosinusitis before surgery nasal volume and MCA is decreased, compared to the one of healthy children. 2. The AR results can be used for the evaluation of the efficiency of the surgical treatment of the rhinosinusitis. [ABSTRACT FROM AUTHOR]