Females have lower salivary flow than males, before and after radiation therapy for head/neck cancer.

OBJECTIVE: To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. RESULTS: Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). CONCLUSIONS: Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.

Oral Candida in post-radiotherapy patients with xerostomia/hyposalivation: A narrative review.

OBJECTIVE: Head and Neck Cancer (HNC) patients receiving radiotherapy (RT) often suffer from xerostomia and/or hyposalivation. As saliva plays an important antimicrobial and cleansing roles, these patients are at higher risks of opportunistic infections. This narrative review aims to provide an overview of current evidence on oral Candida colonisation and infection in these patients. METHODS: A literature review of clinical studies on oral Candida colonisation and candidiasis in HNC patients receiving radiotherapy/chemoradiotherapy was conducted. RESULTS: Many clinical studies found high levels of Candida colonisation and a substantial proportion of post-RT HNC patients suffering from oropharyngeal candidiasis (OPC). Importantly, oral Candida could be a reservoir for life-threatening systemic infection in immunocompromised patients. The rising prevalence of non-albicans Candida species and drug-resistant infections has made identification of Candida species and antifungal susceptibility more important. Recent advances in oral microbiome and its interactions with Candida are discussed. This review also offers perspectives on limitations of current evidence and suggestions for future research. CONCLUSION: Further research to better understand Candida carriage, microbiome, OPC, and xerostomia/hyposalivation post-RT would aid in devising a more comprehensive long-term management plan and novel therapeutic approaches for HNC patients to achieve the full benefits of RT while minimising side effects.

Diagnosis and Dental Management of a Patient With Forbes Albright Syndrome: A Report of a Rare Case.

Forbes Albright syndrome is a hyperprolactinemia syndrome linked to a pituitary tumor associated with galactorrhea and amenorrhea. Cabergoline, an ergot derivative, is its drug of choice. Here, we report the oral manifestations and management of a case of a 32-year-old female, diagnosed and treated with the same. The patient had an alarming increase in the incidence and progression of dental caries. Her diagnosis and management have been highlighted. This can have overbearing effects on the psychology and function of the individual, thus making early diagnosis and precise management important.

PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

Efficacy of lemon mouthwash in improving dry mouth symptoms and salivary flow in hemodialysis patients.

BACKGROUND/AIMS: Gargling mouthwash is a safe and convenient oral care intervention; it rinses the mouth and increases salivary flow rate. The effectiveness of lemon mouthwash in relieving xerostomia and increasing the salivary flow rate among hemodialysis patients has not been studied. Our study sought to analyze the effectiveness of varying concentrations of lemon in mouthwash solutions on xerostomia and salivary flow rate. METHODS: A multi-concentration test was used to assess lemon mouthwash at 20%, 15%, 10%, 5%, and 2.5% concentrations to determine the optimal concentration for relieving dry mouth and increasing salivary flow rate. Generalized estimating equations were used to analyze the differences between various concentrations of lemon mouthwash and bassline values. RESULTS: In total, 44 patients were recruited. The 10% lemon concentration mouthwash was the most effective for increasing salivary flow rate, but the 5% and 2.5% were better accepted by the participants. Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients. CONCLUSIONS: Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients.

A new approach to prevent radiation-induced xerostomia using intraglandular injection of mitochondria-boosting agents.

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.

Oral discomfort and health behavior of patients with typical vs. atypical antipsychotic drugs.

Introduction: Psychiatric patients suffer from oral diseases and side effects of antipsychotic medication. In particular, the typical antipsychotic drugs may cause severe hyposalivation with subsequent oral symptoms. We therefore aimed to compare oral health behavior and oral side effects of in-hospital patients taking typical vs. atypical antipsychotic drugs with the hypothesis that the former drugs cause more oral pain than the newer drugs. Methods: This cross-sectional questionnaire and interview study investigated subjective oral symptoms and their health behavior in 170 hospitalized psychiatric patients, comparing those taking typical vs. atypical antipsychotic drugs. Cross-tabulations and chi-square tests were used for analyses. Results: Persistent oral pain lasting throughout the day was reported by 46% in the typical, and 5% in the atypical antipsychotic group patients, respectively. In both groups, the pain was mainly in the tongue and buccal mucosa and was described as a burning sensation. A significantly higher prevalence of xerostomia was reported in the typical antipsychotic medication group (66%) compared with the atypical antipsychotic medication group (53%, p<0.01). Self-assessed dental health was assessed as poor by two-thirds of the patients of whom 69% reported toothbrushing once daily. Approximately half of them reported having had a visit to a dentist within the previous year. Of the women 28%, and of the men 17%, respectively, had received professional consultations for oral symptoms. Conclusion: The current results on psychiatrically hospitalized patients emphasize the need for awareness of oral discomfort and its subsequent effects on the quality of life in this challenging patient group. Focus should also be placed on a wide range of support encouraging the patients to maintain good daily oral hygiene and seek professional dental help when needed.

Influence of two paraffin wax chewing gums with different con-sistencies on the stimulated salivary flow rate.

This study investigated and compared the consistency and compressive strength of two commercially available paraffin wax chewing gums (Aurosan (AU) and GC Europe (GC)), as well as their impact on stimulated salivary flow rate. Instrumental texture analysis was uti-lized to assess the consistency and compressive strength of AU and GC during a 7-min chewing period. Subsequently, stimulated salivary flow rate (sSFR) was evaluated in healthy subjects using AU and GC over a 7-minute period. The compressive strengths from the pre-liminary test were compared over time with the sialometry data. Eighty-one test subjects, comprising 33 men and 48 women, participated. Over the 7-min measurement period, dif-ferences were observed in the total amount of saliva accumulated per minute. Direct com-parison of AU and GC revealed that regardless of age and gender, the amount of saliva formed after 1 min was 0.63 times less with AU than with GC (95% CI: 0.56 - 0.70; P < 0.001). The accumulated saliva volume with AU was also significantly lower than that with GC in the first 4 min (P = 0.016). However, from minute 5 onwards, the two products no longer showed statistical differences in the total amount of saliva. Comparison of the com-pressive strength of AU and GC showed that the values after 1 and 2 min were significantly higher for AU than for GC (P < 0.05); for all other time points, the compressive strength was higher for GC. In the mixed-effects model after log-transformation of compressive strength and saliva volume, GC exhibited decreasing saliva volumes with increasing compressive strength (P <0.001). Conversely, the opposite was observed for AU (P = 0.019). The study suggests that the consistency or compressive strength of paraffin wax chewing gums from different manufacturers could impact sSFR.

Frequency of Oral Lesions, Olfactory, and Gustatory Disorders and Xerostomia in Patients with COVID-19.

COVID-19, a respiratory illness with a global impact on millions, has recently been linked to manifestations affecting various bodily systems, including the oral cavity. Studies highlight oral issues, like ulcers, blisters, and white patches, alongside olfactory and gustatory dysfunction, influencing an individual's quality of life. In this context, our study aimed to assess the frequency of oral lesions, olfactory and gustatory disorders, and xerostomia resulting from COVID-19. An observational study was conducted with 414 patients to evaluate the frequency of oral symptoms resulting from COVID-19. Patients were diagnosed with mild symptoms and evaluated through clinical examination of the oral cavity and a questionnaire to assess functional alterations. The findings showed that 139 out of 414 patients presented clinical manifestations, with oral lesions being the most prevalent (19.1%), followed by gustatory disorders (18.1%), xerostomia (14.2%), and olfactory dysfunction (14%). The most prevalent oral lesions were ulcerations (n = 51), candidiasis (n = 8), and erythema or red plaques (n = 7). Unfortunately, 50 (12.1%) patients died during this study. Therefore, oral lesions, olfactory and gustatory dysfunctions, and xerostomia are common symptoms associated with COVID-19.

Unlocking the Future: Bioprinting Salivary Glands-From Possibility to Reality.

Salivary gland biofabrication represents a promising avenue in regenerative medicine, aiming to address the challenges of salivary gland dysfunction caused by various factors such as autoimmune diseases and radiotherapy. This review examines the current state of bioprinting technology, biomaterials, and tissue engineering strategies in the context of creating functional, implantable salivary gland constructs. Key considerations include achieving vascularization for proper nutrient supply, maintaining cell viability and functionality during printing, and promoting tissue maturation and integration with surrounding tissues. Despite the existing challenges, recent advancements offer significant potential for the development of personalized therapeutic options to treat salivary gland disorders. Continued research and innovation in this field hold the potential to revolutionize the management of salivary gland conditions, improving patient outcomes and quality of life. This systematic review covers publications from 2018 to April 2024 and was conducted on four databases: Google Scholar, PubMed, EBSCOhost, and Web of Science. The key features necessary for the successful creation, implantation and functioning of bioprinted salivary glands are addressed.

Salivary buffering capacity is correlated with umami but not sour taste sensitivity in healthy adult Japanese subjects.

OBJECTIVE: Saliva serves multiple important functions crucial for maintaining a healthy oral and systemic environment. Among them, the pH buffering effect, which is primarily mediated by bicarbonate ions, helps maintain oral homeostasis by neutralizing acidity from ingested foods. Therefore, higher buffering capacity, reflecting the ability to neutralize oral acidity, may influence taste sensitivity, especially for sour taste since it involves sensing H+ ions. This study aims to explore the relationship between salivary buffering capacity and taste sensitivities to the five basic tastes in healthy adult humans. DESIGN: Eighty seven healthy adult students participated in this study. Resting saliva volume was measured using the spitting method. The liquid colorimetric test was used to assess salivary buffering capacity. The whole-mouth taste testing method was employed to determine the recognition threshold for each tastant (NaCl, sucrose, citric acid, quinine-HCl, monosodium glutamate). RESULTS: Taste recognition thresholds for sour taste as well as sweet, salty, and bitter tastes showed no correlation with salivary buffering capacity. Interestingly, a negative relationship was observed between recognition threshold for umami taste and salivary buffering capacity. Furthermore, a positive correlation between salivary buffering capacity and resting saliva volume was observed. CONCLUSIONS: Salivary buffering capacity primarily influences sensitivity to umami taste, but not sour and other tastes.

Interventional Prospective Studies on Xerostomia in Patients Undergoing Palliative and End-of-Life Care: A Scoping Review.

Patients undergoing palliative care often develop debilitating oral conditions, including xerostomia. These conditions may significantly impact patients' quality of life. Despite the high prevalence and adverse impact of xerostomia, effective management strategies remain unclear. This scoping review was performed to elucidate effective interventions for xerostomia in patients undergoing palliative and end-of-life care. A comprehensive search strategy was employed to identify relevant studies up to August 2023. Full-text primary articles focusing on xerostomia in patients receiving palliative care were included in the review. Eleven articles were selected for analysis, and data were extracted by six reviewers. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among the 11 studies, interventions ranged from oral care to saliva substitutes and methods to stimulate saliva secretion. The primary method of assessing xerostomia was the performance of subjective evaluations using visual analog scale scores or numerical rating scale scores. Various interventions including oral care regimens, topical treatments, and mixed efficacy outcomes were reported. Notably, only one study directly measured the saliva volume, highlighting a reliance on subjective endpoints in most studies. Although no definitive conclusions can be drawn regarding the most effective intervention, oral care was a preferred option for managing xerostomia in patients undergoing palliative care. Additionally, adjunctive treatments such as ice cubes, saline, and moisturizers showed promise but require further investigation. Objective measures should be incorporated into future intervention trials to complement subjective assessments and provide a comprehensive evaluation of xerostomia management strategies in this patient population.

Application of anti-vascular endothelial growth factor antibody restores the function of saliva secretion in a type 2 diabetes mouse model.

OBJECTIVES: Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor (VEGF) antibodies, such as ranibizumab (RBZ), have been used to treat diabetic retinopathy, their effects on the salivary glands are unknown. This study evaluated the effects of RBZ on salivary glands to reduce inflammation and restore salivary function in a mouse model of type 2 diabetes. METHODS: Male KK-Ay mice with type 2 diabetes (10-12 weeks old) were used. The diabetes mellitus (DM) group received phosphate-buffered saline, while the DM + RBZ group received an intraperitoneal administration of RBZ (100 µg/kg) 24 h before the experiment. RESULTS: Ex vivo perfusion experiments showed a substantial increase in salivary secretion from the submandibular gland (SMG) in the DM + RBZ group. In addition, the mRNA expression levels of TNF-α and IL-1ß were considerably lower in this group. In contrast, those of aquaporin 5 were substantially higher in the DM + RBZ group, as revealed by quantitative reverse transcription PCR. Furthermore, the number of lymphocyte infiltration spots in the SMG was notably lower in the DM + RBZ group. Finally, intracellular Ca2+ signaling in acinar cells was considerably higher in the DM + RBZ group than that in the DM group. CONCLUSION: Treating a type 2 diabetic mouse model with RBZ restored salivary secretion through its anti-inflammatory effects.

Periodontal status and mandibular biomechanics in rats subjected to hyposalivation and periodontitis.

Xerostomia emerges as a consequence of salivary gland hypofunction, and seriously compromises the integrity of hard and soft oral tissues, whileperiodontitis is an infectious disease characterized by biofilm accumulation, inflammation and alveolar bone resorption. AIM: The aim this study was to compare the deleterious effects caused by experimental hyposalivation, periodontitis, and the combination of both on periodontal tissues and mandibular biomechanics in rats. MATERIALS AND METHOD: Hyposalivation (group H) was induced through bilateral submandibulectomy. Periodontitis (group EP) was induced by injecting LPS (1 mg/ml) into the gingiva of the first lower molars. A third group was subjected to both conditions (group H+EP). Alveolar bone loss was evaluated by micro-computed tomography and histomorphometric analysis, and gingival inflammatory mediators were assessed by specific techniques. Biomechanical properties were evaluated in mandible. RESULTS: Alveolar bone loss increased similarly in groups H, EP and H+EP compared to control. Metalloproteinase (MMP2 and MMP9) activity was similar in H and control, but higher in groups EP and H+EP (MMP2: C 9644+2214, EP 34441+3336, H 5818+1532, H+EP 42673+3184; MMP9: C 5792+961, EP 14807+861, H 9295+520, H+EP 4838+1531). The rest of the inflammatory mediators evaluated increased in groups H, EP and H+EP to a greater or lesser extent with respect to the control, although in most cases, they were higher in groups EP and H+EP than in group H. The biomechanical properties of the mandible increased in group H compared to the other three groups. CONCLUSIONS: Both hyposalivation and periodontitis cause periodontal damage, but hyposalivation also produces biomechanical alterations, causing more extensive deleterious effects than periodontitis.

La xerostomía surge como consecuencia de la hipofunción de las glándulas salivales y compromete seriamente la integridad de los tejidos orales duros y blandos, mientras que la periodontitis es una enfermedad infecciosa caracterizada por la acumulación de biofilm, inflamación y reabsorción ósea alveolar. OBJETIVO: El objetivo del presente estudio fue comparar los efectos deletéreos causados por la hiposalivación y la periodontitis experimental, y la combinación de ambas sobre los tejidos periodontales y la biomecánica mandibular en ratas. MATERIALES Y MÉTODOS: La hiposalivación (H) se indujo mediante una submandibulectomía bilateral. Por otra parte, la periodontitis (PE) se indujo mediante la inyección de LPS (1 mg/ml) en la encía de los primeros molares inferiores. Otro grupo se sometió a ambas condiciones (H+PE). La pérdida ósea alveolar se evaluó mediante tomografia microcomputarizada y análisis histomorfométrico, mientras que los mediadores inflamatorios gingivales fueron determinados mediante técnicas específicas. Se evaluaron las propiedades biomecánicas en la mandíbula. RESULTADOS: La hiposalivación aumentó la pérdida ósea alveolar en comparación con el control de forma similar a la PE y H+PE. La actividad de las metaloproteinasas (MMP2 y MMP9) fue similar en los grupos H y control, pero resultó mayor en los grupos PE y H+PE (MMP2: C 9644+2214, PE 34441+3336, H 5818+1532, H+PE 42673+3184; MMP9: C 5792+961, PE 14807+861, H 9295+520, H+PE 24838+1531). El resto de los mediadores inflamatorios evaluados aumentaron en mayor o menor medida en los grupos H, PE y H+PE respecto al control, aunque en la mayoría de los casos fueron superiores en los grupos PE y H+PE respecto al grupo H. Sin embargo, las propiedades biomecánicas de la mandíbula aumentaron en el grupo H con respecto a los otros grupos. CONCLUSIONES: Tanto la hiposalivación como la periodontitis causan daño periodontal, pero la hiposalivación también produce alteraciones biomecánicas, provocando efectos deletéreos más extensos que la periodontitis.

Enhancing Intraoral Fluoride Retention in Older Adults: A Randomized Crossover Study.

INTRODUCTION: Previous studies have shown that a calcium prerinse can increase intraoral fluoride retention from a fluoride rinse. To explore the potential of this approach to control root caries, we assessed intraoral fluoride bioavailability after a calcium prerinse in older adults with normal to low salivary flow rates. METHODS: In a 2-period crossover trial (NCT04239872), 20 participants (65-80 y old), with low or normal salivary flow rate, rinsed for 1 min with a 0.05% NaF mouth rinse (226 ppm F, F only) or with this rinse immediately after a 1-min rinse with 150 mM calcium lactate (Ca→F). Dental biofilm and saliva samples were collected before and up to 2 h after the rinse(s). Fluoride concentrations in saliva (whole and clarified) and dental biofilm (fluid and solid phases) were blindly determined. Data were statistically analyzed by a mixed-effects model for the effect of treatment, time, and their interaction (α = 5%). RESULTS: The Ca→F group resulted in significantly higher fluoride concentrations in all variables analyzed, for almost all of the collection time points. The effect was greater in the biofilm solids and whole saliva (compatible with the formation of calcium fluoride deposits) and still significant (P < 0.001) after 2 h in the biofilm fluid and clarified saliva, suggesting that fluoride stored in insoluble particles was released, increasing free fluoride. CONCLUSION: The use of a calcium prerinse before a fluoride rinse was able to prolong intraoral fluoride bioavailability in older adults. KNOWLEDGE TRANSFER STATEMENT: A calcium prerinse increased intraoral fluoride bioavailability in older individuals. This approach could be used to improve root caries control without the need to increase the fluoride concentration in dental products.

Dry Mouth Dilemma: A Comprehensive Review of Xerostomia in Complete Denture Wearers.

Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life. This review explores the relationship between saliva and complete dentures, highlighting the varied management strategies for xerostomia. Saliva plays a critical role in denture retention, lubrication, and oral environment buffering. Complete denture wearers often experience reduced salivary flow, aggravating symptoms of xerostomia. Various management approaches are discussed, including general measures such as hydration and salivary stimulation techniques which aim to boost saliva production naturally. The use of salivary substitutes provides artificial lubrication and moisture to alleviate dry mouth discomfort. Oral lubricating devices, such as sprays, gels, and lozenges, offer relief by mimicking saliva's lubricating properties, thereby improving denture stability and comfort. This review addresses the etiology of xerostomia in complete denture wearers and explores preventive measures to reduce its impact. A comprehensive approach has been discussed for the management of xerostomia which will help to improve the oral health and well-being of complete denture wearers experiencing dry mouth.

On the rheological and sensory properties of a novel natural salivary substitute.

The prevalence of xerostomia, the sensation of dry mouth, is estimated at 20 % in the general population and up to 50 % in older adults. Saliva plays different roles during bolus formation: lubrication, mixing, coating, hydration, dissolution, and comminution of food particles. This study proposes and tests artificial saliva formulations mimicking human saliva rheological and sensory perceptions. Shear and extensional rheology were assessed to select the type of formulation closest to saliva rheological characteristics. After evaluating three alternative sources, an extract simulating saliva rheology was produced from flax seeds. Friction coefficient and rheological properties, such as flow curves, relaxation times, and Trouton ratios, were compared favorably with human saliva. The sensory evaluation demonstrated that flaxseed extracts induce perceived mouth hydration, slipperiness, and adhesion exceeding that of human saliva. The flaxseed extract proposed in this can i) be used to study in vitro food oral processing and ii) pave the way to novel natural salivary substitutes to alleviate the symptoms of xerostomia.

Validation of the Korean version of the Summated Xerostomia Inventory among older adults residing in nursing homes.

BACKGROUND: Xerostomia is commonly experienced by older individuals. We sought to develop and evaluate the reliability and validity of the Korean version of the Summated Xerostomia Inventory (K-SXI) among older adults residing in long-term care facilities (LTCFs) in Korea. METHODS: In this secondary data analysis study using cross-sectional data, a cross-cultural adaptation process was conducted for the Korean version before data collection. Data collection was conducted from July 2021 to January 2022, targeting 544 older adults in 16 LTCFs. Data analysis included intraclass correlation coefficient (ICC) for test-retest reliability, and Cronbach's α for internal consistency reliability. Exploratory and confirmatory factor analyses were used to verify construct and convergent validity. Test-retest analysis was performed 6 weeks after baseline. Convergent and concurrent validities were assessed with age group and the xerostomia standard single question, respectively. RESULTS: A total of 544 older adults participated in this study. The mean of total K-SXI score was 11.70 (standard deviation, 4.96) points. The ICC value was calculated to be 0.90, and Cronbach's α of K-SXI was 0.92. Exploratory factor analysis revealed a single factor, explaining 74.8% of the total variance, however, some goodness-of-fit indices of the single factor model were found to be unsuitable in confirmatory factor analysis. The convergent and concurrent validity were supported. CONCLUSION: The present study provides evidence supporting the validity and reliability of the K-SXI for measuring xerostomia in institutionalized older adults in Korea.

Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going.

Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([177Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [177Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies. Further, the drug development pipeline is deep with variations of PSMA-targeting radionuclides, including higher energy alpha particles conjugated to PSMA-honing vectors. It is safe to assume that an increasing number of patients will be exposed to PSMA-targeted radiopharmaceuticals during the course of their cancer treatment. In this setting, it is important to better understand and mitigate the most commonly encountered toxicities. One particularly vexing side effect is xerostomia. In this review, we discuss the scope of the problem, inventories to better characterize and monitor this troublesome side effect, and approaches to preserve salivary function and effectively palliate symptoms. This article aims to serve as a useful reference for prescribers of PSMA-targeted radiopharmaceuticals, while also commenting on areas of missing data and opportunities for future research.

Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology.

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.