Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment.

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24 h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

[The Comparative Effectiveness of Using Cold Water Oral Spray and Cold Saline Oral Spray for Thirst Relief in Patients With Endotracheal Intubation in the Intensive Care Unit].

BACKGROUND: Thirst is a common symptom among patients with endotracheal intubation in the intensive care unit (ICU), with an estimated prevalence of 88%. PURPOSE: This study was designed to compare the effectiveness of cold saline spray and cold water spray in alleviating thirst, and to explore the maintenance and sustained effects of both groups in relieving thirst among patients with endotracheal intubation in the ICU. METHODS: Patients with indwelling tracheal tubes in the medical ICU were recruited from one medical center in northern Taiwan and randomly assigned to either the cold saline (n = 18) or cold water (n = 18) group. The cold saline group received three rounds of cold saline spray at a temperature of 2°C - 8°C. Each round consisted of 10 sprays directed toward each of the four surfaces of the oral cavity followed by a 5-minute wait period. This process was repeated three times, with 30-minute intervals between interventions. The cold water group received the same intervention steps using a cold water spray at 2°C - 8°C. Thirst intensity was measured using a numeric rating scale before and after each of the three interventions in both groups. Demographic and relevant physiological data were collected on the participants by reviewing their medical records. RESULTS: Both of the interventions were found to effectively alleviate thirst intensity, with no significant difference between the two groups in terms of thirst intensity reduction after each intervention detected. Only the cold water spray had a maintenance effect, while the two groups had a continuous sustained effect in alleviating thirst intensity. CONCLUSIONS: Both of the interventions effectively alleviated thirst, and the cold water spray had both maintenance and sustained effects in alleviating thirst intensity. Based on the results, the cold water spray method may be considered as the priority treatment for thirst alleviation by healthcare providers in the clinical management of patients with tracheal intubation.

Evaluation the efficacy and safety of N-acetylcysteine inhalation spray in controlling the symptoms of patients with COVID-19: An open-label randomized controlled clinical trial.

The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C-reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus-2 is limited and further research is required.

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial.

BACKGROUND: The aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT). METHODS: Prior to RCT, the effect of trehalose (5-20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions. RESULTS: In the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05). CONCLUSIONS: The 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

[Efficacy of Sildenafil oral spray for the treatment of erectile dysfunction in patients with type 2 diabetes mellitus and prediabetes].

AIM: To evaluate the results of using Sildenafil in the form of an oral spray (Gent) for the treatment of erectile dysfunction (ED) in men with type 2 diabetes mellitus (DM) and prediabetes. MATERIAL AND METHODS: A total of 60 patients were divided into two groups of 30 people. The group 1 included patients with prediabetes, while group 2 consisted of patients with type 2 DM. All men had proven ED. The severity of ED was assessed using the International Index of Erectile Function (IIEF-5). To assess the state of penile blood flow, all patients underwent Doppler ultrasound before and after treatment. Patients with prediabetes used Sildenafil in the form of oral spray (Gent) 25 mg (2 doses) 1 time per day for 1 month, patients with type 2 diabetes received 50 mg (4 injections) every other day for 1 month. In addition, most of the subjects took metformin and followed diet therapy. RESULTS: In patients of both groups, the administration of Sildenafil oral spray led to a decrease in body weight, waist circumference, a decrease in insulin and Hemoglobin A1C level without changing of hypoglycemic therapy in those with type 2 DM. In men with prediabetes, a decrease in fasting insulin levels was found. During treatment, half of the persons with impaired glucose metabolism had an increase in the testosterone level. According to IIEF-5, a decrease in the severity of ED in both groups of patients was seen. In men with prediabetes, the average IIEF-5 score increased from 15.98 to 21.57 points (p<0.05), while in patients with type 2 DM it improved from 12.18 to 18.44 points (p<0.05). Doppler ultrasound indicated a significant increase in the maximum systolic blood flow velocity and arterial resistivity index after treatment with Sildenafil oral spray in patients with both prediabetes and type 2 diabetes. CONCLUSION: Sildenafil oral spray can be effectively used for the treatment of ED in men with type 2 DM and prediabetes.

The effects of a combination oral spray (Mucosamin®) for the prevention of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation: a double blind randomized clinical trial.

PURPOSE: Oral mucositis (OM) is a frequent complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Damage to the nuclear and non-nuclear materials of the mucosal cells by the production of Reactive Oxygen Species (ROS) and proinflammatory cytokines could result to development and progression of OM. Previous studies have shown the effectiveness of Mucosamin® oral spray in the management of pain and acceleration of OM healing. The aims of the current study were to evaluate prophylactic effects of Mucosamin® oral spray in reducing the incidence and severity of OM in pediatric patients undergoing allogeneic HSCT. METHOD: The current study was designed as a double-blind, placebo-controlled randomized clinical trial. Sixty patients were enrolled in the study and received placebo or Mucosamin® spray. Patients in both groups used sprays 4 times daily. Product application was begun at the time of initiation of conditioning regimen and was continued for 14 days. RESULTS: Mucosamin® significantly reduced incidence and severity of OM compared to the placebo (P values: 0.027 and 0.035, respectively). This product could also decrease OM duration and delay OM onset (P values: 0.007 and 0.006, respectively). CONCLUSION: Mucosamin® could effectively reduce incidence, severity, and duration of OM and delay OM onset in pediatric patients undergoing allogeneic HSCT. TRIAL REGISTRATION: The study protocol was registered in the Iranian Registry of Clinical Trials under the registry number IRCT20190917044805N1.

In vitro effect of an oral spray and mouthrinses on dual species cariogenic bacteria biofilm.

PURPOSE: To determine the efficacy of an oral spray and oral rinses to inhibit oral cariogenic dual species biofilm formation on hydroxyapatite (HA) discs. METHODS: The Streptococcus mutans (NCTC 10449, ATCC), Lactobacilli casei (NCIB 8820, ATCC) dual species biofilm formation and inhibition on HA disc was tested using five antimicrobial products, i.e., oral spray (Oral Shield), Mouthrinse (Listerine Ultra Clean, Listerine Cool Mint, Crest Pro-Health, ACT Restoring). An untreated group served as control. The established biofilm on the surface of each disc was treated or untreated with oral spray and mouthrinse for 2 minutes after 24 or 48 hours. The dual species biofilm formation and inhibition on HA discs was determined using the spread plate method and colonies were counted and expressed as colony forming units (CFU/mL). Further, the HA disc was subjected to confocal laser scanning microscope (CLSM) examination to determine the viability of cells using live-dead staining and a scanning electron microscope (SEM) to examine the effect on bacteria biofilm and morphology. The cytotoxic effect of test spray and mouthrinse was tested on OKF6/TERT-2 cells using the MTT method. RESULTS: At each time point, 24- or 48-hours, S. mutans and L. casei mixed biofilm on HA discs had a significantly (P> 0.001) fewer number of bacteria in the treated groups than the untreated one. The oral spray and mouthrinses had a detrimental effect on bacteria biofilm, morphology and cell wall, whereas no significant changes were observed in the untreated group. Cytotoxic assay revealed that the oral spray was safe for human oral keratinocyte cells. CLINICAL SIGNIFICANCE: The tested oral spray could offer potential to inhibit the cariogenic bacteria and protect the tooth enamel from cariogenic bacterial biofilm.

A randomised clinical trial on the effect of oral antimicrobial sprays in institutionalised elders.

OBJECTIVE: To compare the effectiveness of chlorine dioxide, chlorhexidine and placebo sprays in improving oral hygiene among institutionalised elders. BACKGROUND: Available evidence suggests that oral sprays may be an effective alternative delivery method for plaque control; however, few studies have evaluated antimicrobial agents other than chlorhexidine. MATERIALS AND METHODS: A total of 228 elders across 11 nursing homes in Hong Kong were recruited into the clinical trial. Participants were randomly allocated into one of the following groups: 0.1% pH-balanced chlorine dioxide spray, 0.2% chlorhexidine spray or sterile water spray (placebo control), once daily. Dental plaque, gingival bleeding and other clinical oral health outcomes were assessed at baseline, 3 and 6 months. Participant acceptability of the interventions was assessed at the end of the clinical trial. RESULTS: Review assessments were conducted for 135 elders at 6 months. Significantly greater reductions in plaque index scores were observed with the chlorhexidine spray (0.4) and chlorine dioxide spray (0.3) than the placebo spray (0.1). While significant reductions in gingival bleeding scores were observed within the chlorhexidine (7.4), chlorine dioxide (7.5) and placebo (5.3) sprays after 6 months, change scores were not significantly different between groups. Significantly greater increases in the levels of staining were observed in the chlorhexidine spray group (-0.1) than the chlorine dioxide (0.0) and placebo spray (0.0) groups. CONCLUSION: Antimicrobial sprays were shown to be effective among institutionalised elders. Chlorine dioxide spray showed equivalent effects on dental plaque and gingival bleeding relative to the chlorhexidine spray over a 6-month period.

Carrageenan-containing over-the-counter nasal and oral sprays inhibit SARS-CoV-2 infection of airway epithelial cultures.

Pharmaceutical interventions are urgently needed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission. As SARS-CoV-2 infects and spreads via the nasopharyngeal airways, we analyzed the antiviral effect of selected nasal and oral sprays on virus infection in vitro. Two nose sprays showed virucidal activity but were cytotoxic precluding further analysis in cell culture. One nasal and one mouth spray suppressed SARS-CoV-2 infection of TMPRSS2-expressing Vero E6 cells and primary differentiated human airway epithelial cultures. The antiviral activity in both sprays could be attributed to polyanionic ι- and κ-carrageenans. Thus, application of carrageenan-containing nasal and mouth sprays may reduce the risk of acquiring SARS-CoV-2 infection and may limit viral spread, warranting further clinical evaluation.

Cannabinoids in glioblastoma multiforme-hype or hope?

Cannabis and its derivatives are being used increasingly by patients with cancer, including patients with glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy. Despite promising preclinical data suggesting potential anti-cancer effects for cannabinoids in GBM, clinical and safety data are lacking. This editorial will discuss a recent Phase 1b trial of nabiximols oromucosal spray in combination with dose-intense temozolomide in patients with recurrent GBM in the context of other relevant findings in this field.

A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma.

BACKGROUND: Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM. METHODS: Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored. RESULTS: The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK. CONCLUSIONS: With personalised dosing, nabiximols had acceptable safety and tolerability with no drug-drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: Part 1- NCT01812603; Part 2- NCT01812616.

Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience.

BACKGROUND: This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications. METHODS: Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months. RESULTS: Mean 0-10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks' range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile. CONCLUSIONS: More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.

Sites in the oropharynx reached by different methods of using mouthwash: clinical implication for oropharyngeal gonorrhoea prevention.

OBJECTIVES: Oropharyngeal gonorrhoea is increasing among men who have sex with men and is commonly found in the tonsils and at the posterior pharyngeal wall. To address this rise, investigators are currently trialling mouthwash to prevent oropharyngeal gonorrhoea. We aimed to determine which parts of the oropharynx were reached by different methods of mouthwash use (oral rinse, oral gargle and oral spray). METHODS: Twenty staff at Melbourne Sexual Health Centre participated in the study from March to May 2018. Participants were asked to use mouthwash mixed with food dye, by three application methods on three separate days: oral rinse (15 s and 60 s), oral gargle (15 s and 60 s) and oral spray (10 and 20 times). Photographs were taken after using each method. Three authors assessed the photographs of seven anatomical areas (tongue base, soft palate, uvula, anterior tonsillar pillar, posterior tonsillar pillar, tonsil, posterior pharyngeal wall) independently and scored the dye coverage from 0% to 100%. Scores were then averaged. RESULTS: The mean coverage at the sites ranged from 2 to 100. At the posterior pharyngeal wall, spraying 10 times had the highest mean coverage (29%) and was higher than a 15 s rinse (2%, p=0.001) or a 15 s gargle (8%, p=0.016). At the tonsils, there was no difference in mean coverage between spray and gargle at any dosage, but spraying 20 times had a higher mean coverage than a 15 s rinse (42% vs 12%, p=0.012). CONCLUSION: Overall, spray is more effective at reaching the tonsils and posterior pharyngeal wall compared with rinse and gargle. If mouthwash is effective in preventing oropharyngeal gonorrhoea, application methods that have greater coverage may be more efficacious.

Derivation of cancer no significant risk levels and screening safety assessment for 2-nitropropane in spray products.

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log-probit, log-logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 µg/day and 32 µg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2-NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2-NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1-nitropropane where 2-NP is a minor contaminant.

Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial.

Objective: To determine whether differences in disability status, spasticity severity, and spasticity duration at treatment start in patients with resistant multiple sclerosis (MS) spasticity might influence response to add-on tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (nabiximols) versus further re-adjustment of optimized first-line antispasticity medication.Methods: Using the database from the Sativex® as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) study, this post hoc analysis evaluated spasticity severity (0-10 numerical rating scale [NRS] scores) and pain severity (0-10 NRS scores) evolution from randomization (baseline) to week 12 (end of double-blind treatment) in defined subgroups: Expanded disability status scale [EDSS] score subgroups (<6 and ≥6); spasticity severity 0-10 NRS score subgroups (4 to ≤6 and >6), and spasticity duration subgroups (<5 and ≥5 years).Results: THC:CBD oromucosal spray (nabiximols) halved mean severity scores for spasticity and pain in all subgroups. Active treatment significantly improved mean spasticity severity scores versus placebo from week 4 onwards in both EDSS subgroups, in the severe spasticity subgroup, and in both spasticity duration subgroups. Active treatment significantly improved mean pain severity scores versus placebo in the ≥6 EDSS subgroup, in the severe spasticity subgroup and in both spasticity duration subgroups.Conclusion: Add-on THC:CBD oromucosal spray (nabiximols) consistently relieves resistant spasticity across subgroups defined by baseline EDSS score, spasticity severity NRS score and spasticity duration. Patients with moderate resistant MS spasticity benefit numerically from treatment; patients with severe resistant spasticity achieve significant therapeutic gains. Spasticity-associated pain often improves similarly in the same subgroups.

Spray drying OZ439 nanoparticles to form stable, water-dispersible powders for oral malaria therapy.

BACKGROUND: OZ439 is a new chemical entity which is active against drug-resistant malaria and shows potential as a single-dose cure. However, development of an oral formulation with desired exposure has proved problematic, as OZ439 is poorly soluble (BCS Class II drug). In order to be feasible for low and middle income countries (LMICs), any process to create or formulate such a therapeutic must be inexpensive at scale, and the resulting formulation must survive without refrigeration even in hot, humid climates. We here demonstrate the scalability and stability of a nanoparticle (NP) formulation of OZ439. Previously, we applied a combination of hydrophobic ion pairing and Flash NanoPrecipitation (FNP) to formulate OZ439 NPs 150 nm in diameter using the inexpensive stabilizer hydroxypropyl methylcellulose acetate succinate (HPMCAS). Lyophilization was used to process the NPs into a dry form, and the powder's in vitro solubilization was over tenfold higher than unprocessed OZ439. METHODS: In this study, we optimize our previous formulation using a large-scale multi-inlet vortex mixer (MIVM). Spray drying is a more scalable and less expensive operation than lyophilization and is, therefore, optimized to produce dry powders. The spray dried powders are then subjected to a series of accelerated aging stability trials at high temperature and humidity conditions. RESULTS: The spray dried OZ439 powder's dissolution kinetics are superior to those of lyophilized NPs. The powder's OZ439 solubilization profile remains constant after 1 month in uncapped vials in an oven at 50 °C and 75% RH, and for 6 months in capped vials at 40 °C and 75% RH. In fasted-state intestinal fluid, spray dried NPs achieved 80-85% OZ439 dissolution, to a concentration of 430 µg/mL, within 3 h. In fed-state intestinal fluid, 95-100% OZ439 dissolution is achieved within 1 h, to a concentration of 535 µg/mL. X-ray powder diffraction and differential scanning calorimetry profiles similarly remain constant over these periods. CONCLUSIONS: The combined nanofabrication and drying process described herein, which utilizes two continuous unit operations that can be operated at scale, is an important step toward an industrially-relevant method of formulating the antimalarial OZ439 into a single-dose oral form with good stability against humidity and temperature.

Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a oral spray for children with recurrent streptococcal pharyngotonsillitis: a randomized placebo-controlled clinical study.

PURPOSE: Group A beta-hemolytic Streptococcus (GABHS) causes a recurrent acute pharyngotonsillitis (RAPT) in children. Moreover, the repeated use of antibiotics contributes to its resistance. However, S. Salivarius 24SMB and S. oralis 89a were effective probiotics in other infections. Thus, we decided to evaluate this combination efficacy compared to placebo in RAPT. METHODS: Patients with microbiologically confirmed GABHS were enrolled in this randomized, placebo-controlled trial. They received the aforementioned combination or placebo as an oral spray. We investigated episodes of frequency and duration, need for antibiotics, school days lost, the treatment impact on life quality, treatment compliance and side effects during a 90-day treatment and a 6-month follow-up. RESULTS: We included 41 patients in each group. The mean number of GABHS infection was significantly lower during both study periods for the two groups. However, our treatment group showed a lower rate. Moreover, the probiotic group had a lower mean number and a shorter median duration of GABHS episodes during both study periods than controls. Furthermore, the mean duration of antibiotic treatment was lower in the probiotic group during the 90-day and 6-month follow-up periods. Similarly, patients in the probiotic group showed a significantly lower mean number of absence days from school but higher EQ-VAS score. Indeed, all patients included were compliant to treatment. CONCLUSIONS: We identified potential probiotics, possessing desirable features against GABHS pharyngotonsillitis. Our findings represent the first evidence which throws the light on using these probiotics that can reduce antibiotics use which did not have efficient results regarding recurrence.

Effectiveness of a spray containing 1% malic acid in patients with xerostomia induced by graft-versus-host disease.

BACKGROUND: To evaluate the clinical effectiveness of a topical sialogogue spray (malic acid, 1%) in the treatment of xerostomia in patients with chronic Graft versus Host Disease (cGVHD). MATERIAL AND METHODS: This study was designed as a randomized double-blind clinical study. Twenty-eight patients with cGVHD suffering from xerostomia were divided into 2 groups: the first group (14 patients) received a topical sialagogue spray containing malic acid 1% (SalivAktive®) whereas the second group (14 patients) received a placebo. Both groups received treatment for 2 weeks. Dry Mouth Questionnaire (DMQ) scores and unstimulated salivary flows rate were collected before and after treatment. RESULTS: DMQ scores increased significantly from 1.3 ± 0.4 to 3.5 ± 0.4 points (p<0.05) after two weeks of treatment with malic acid, whereas in the control group DMQ scores increased from 1.2 ± 0.7 points to 1.4 ± 0.6 (p>0.05). The unstimulated salivary flow rate in patients treated with malic acid increased significantly from 0.15 ± 0.06 mL/min to 0.24± 0.08 mL/min, while that of the patients treated with placebo went from 0.16 ± 0.07 mL/min to 0.17 ± 0.09 mL/min (p>0.05). CONCLUSIONS: Malic acid 1% spray can be considered effective in the treatment of GVHD induced xerostomia.

The effect of antiseptic oral sprays on dental plaque and gingival inflammation: A systematic review and meta-analysis.

OBJECTIVES: To review the effectiveness of antiseptic oral sprays on oral health. METHODS AND MATERIALS: Three electronic databases (PubMed, Cochrane Library and Web of Science) were systematically searched to identify relevant studies. Only randomized controlled trials (RCTs) comparing the effect of oral sprays to placebo/control spray or mouthrinse on dental plaque and gingival inflammation were included. RESULTS: Among a total of 996 papers, 20 effective studies fulfilled the selection criteria, and 8 studies were suitable for inclusion in meta-analyses. A meta-analysis of three studies using a 0.2% chlorhexidine (CHX) spray intervention, without prophylaxis at baseline, showed reductions in Plaque Index (PI) (Silness and Löe) and Gingival Index (GI) (Silness and Löe) scores of 0.74 (95% CI: -1.03 to -0.45) and 0.22 (95% CI: -0.38 to -0.06), respectively. Five studies provided a prophylaxis for subjects before study initiation. Three of these five studies used 0.2% CHX spray. A meta-analysis demonstrated an increase of 0.18 (95% CI: -0.01 to 0.37) in PI (Silness and Löe) scores. Two RCTs compared 0.12% and 0.2% CHX spray, and a meta-analysis showed increases of 1.71 (95% CI: 1.27 to 2.14) and 1.58 (95% CI: 1.23 to 1.93), respectively, in PI (Quigley and Hein) scores. Of the RCTs not amenable to meta-analysis, eight studies reported significant improvements in PI and GI scores. CONCLUSIONS: Available evidence suggests that oral sprays are an acceptable delivery method for antiseptic agents. Further high-quality studies are warranted to determine the effectiveness of alternative chemotherapeutic agents delivered via oral sprays on oral health.

Treatment of symptomatic oral mucositis with sodium hyaluronate and synthetic amino acid precursors of collagen in patients undergoing haematopoietic stem cell transplantation.

The purpose of the study is to evaluate the clinical effects of Mucosamin® (a spray preparation containing sodium hyaluronate combined with a pool of amino acids of precursor collagen, including L-Proline, L-Leucine, L-Lysine and glycine) on wound healing and pain management of oral mucositis after hematopoietic stem cell transplantation. The importance of professional dental hygiene by dental hygienist in reducing the severity of oral mucositis as unique therapy or in addition to therapy with Mucosamin® was also evaluated. One hundred thirty-seven patients undergoing hematopoietic stem cell transplantation were recruited in a case-control study and divided into 4 groups: Group A: professional oral hygiene + Mucosamin®; Group B: professional oral hygiene + standard treatment with chlorhexidine 0.20%;; Group C: only Mucosamin®; Group D: only standard treatment with chlorhexidine 0.20%. The following evaluations were made: WHO mucositis scale, OMAS mucositis scale, VAS, periodontal recording, days of mucositis. Comparing the groups at the onset of OM on WHO scale, it was observed that Group A grade 1 occurrence was more statistically significant than Group B (p= 0.03*); comparison between Group A and D showed a statistically significant difference in favour of Group A (p= 0.0002*). Also OMAS scale showed a statistically significant difference between groups who assumed Mucosamin, who developed lower OM grade (p = 0.001*). There was a statistically significant difference between group A compared with group B over the overall duration of OM (p = 0.02*), as well as between group A and group D (p=0.03*). According to the present study the combination of a careful debridement, correct oral hygiene during hospitalization and the use of Mucosamin® exponentially reduces the severity and duration of mucositis and consequently the discomfort of the patient. Moreover, it can be stated that the use of Mucosamin® also results in a reduction in the extent of chemotherapy lesions. Hyaluronic acid and amino acid-based sprays can be a valuable therapeutic aid in the treatment of mucositis.