A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-ß and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis.

PURPOSE: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. METHODS: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-ß and IL-1. RESULTS: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-ß significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. CONCLUSION: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Budesonide nasal irrigation improved Lund-Kennedy endoscopic score of chronic rhinosinusitis patients after endoscopic sinus surgery.

PURPOSE: Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS. METHODS: Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund-Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale. RESULTS: Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different. CONCLUSIONS: Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.

Formulation, functional evaluation and ex vivo performance of thermoresponsive soluble gels - A platform for therapeutic delivery to mucosal sinus tissue.

Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8°C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature (≈34°C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses.

A double-blind randomized controlled trial of normal saline, lactated Ringer's, and hypertonic saline nasal irrigation solution after endoscopic sinus surgery.

BACKGROUND: Nasal douching is commonly performed after endoscopic sinus surgery (ESS). There is a lack of studies comparing the clinical effect of various douching solutions after ESS. This study investigated the clinical effects of normal saline, lactated Ringer's, and hypertonic saline nasal douching solutions after ESS. METHODS: Adult patients (41.8 ± 12.9 years) undergoing bilateral ESS for chronic rhinosinusitis at a single tertiary referral center were blindly randomized to one of the three study solutions and reviewed on postoperative weeks 1, 3, and 6. The 20-item Sino-Nasal Outcome Test (SNOT-20) scores, visual analog scale (VAS) symptom scores, digital video capture of the sinus cavities, and mucociliary clearance (MCC) times were performed at each visit. The mucosa appearances were scored by a second investigator, blinded to the douching solution. RESULTS: Seventy-four patients were recruited. All groups showed an improvement with treatment in SNOT-20 scores and VAS scores, as well as endoscopic evaluation of mucosa appearance over time. There was no improvement of MCC during the treatment period. Irrigation with lactated Ringer's solution resulted in better symptom scores in SNOT-20 (p < 0.05) and VAS (p < 0.05), compared with irrigation with normal saline or hypertonic saline solutions. Patients receiving hypertonic saline solutions had less polypoidal mucosa at week 6. CONCLUSION: Douching with lactated Ringer's solution after ESS results in better improvement in sinonasal symptoms, compared with normal saline or hypertonic saline solutions.

Nasal corticosteroid treatment reduces substance P levels in tear fluid in allergic rhinoconjunctivitis.

BACKGROUND: The mechanisms underlying conjunctival symptom reduction by nasal corticosteroids in allergic rhinoconjunctivitis are unknown. A naso-ocular reflex may be present. OBJECTIVE: To study the effects of nasal fluticasone furoate (FF) on conjunctival symptoms and substance P and histamine levels in tear fluid after nasal grass pollen provocation (GPP). METHODS: A double-blind placebo-controlled study was performed in 26 grass pollen-allergic patients. A selective GPP was performed during the grass pollen season after 2 weeks of FF or placebo treatment. Nasal and conjunctival symptoms were scored using a visual analog scale (VAS), and tear fluid was collected for measuring substance P and histamine using an enzyme-linked immunosorbent assay. RESULTS: Compared with placebo, FF reduced conjunctival symptom scores during the pollen season (-1.75 [-2.75, 0.20] vs 0.0 [0.0, 0.0]; P = .01) and after GPP at 15 minutes (0.05 [-0.42, 1.52] vs 2.05 [0.62, 3.62]; P < .001) and 1 hour (-0.45 [-1.75, 0.1] vs 0.05 [-0.97, 1.85]; P < .01). Treatment with FF decreased substance P levels in tear fluid (44.11 [32.81, 61.02] vs 65.26 [48.62, 79.73] pg/mg protein; P = .0098). Histamine levels in tear fluid showed a GPP-induced increase in the placebo group (7.26 [3.12, 9.69] vs 5.71 [2.05, 7.00] ng/mg protein; P = .02), but not in the FF group (6.77 [3.43, 13.00] vs 5.24 [3.18, 7.06] ng/mg protein; P = .08). CONCLUSION: FF nasal spray reduced conjunctival symptoms in grass pollen-allergic patients in parallel with lower substance P levels in tear fluid. These data help in understanding the reduction of conjunctival symptoms by intranasal anti-inflammatory therapy.