Dysphagia Research Articles

Clinical profile of neonates with polycythemia at a tertiary care hospital in North East, India

Background: Neonatal polycythemia (NPC) is associated with hyper viscosity of blood causing impairment of tissue oxygenation, perfusion and formation of microthrombi. Polycythemia is defined as a venous hematocrit (Hct) of≥65% or a haemoglobin (Hb)>22g/dl. It presents with a nonspecific clinical features like plethora, poor feeding, lethargy, hypoglycaemia, jaundice. The aim of this study was to assess the clinical profile in neonates with polycythemia admitted in the paediatrics ward of a tertiary care centre in North East, India. Methods: A hospital based cross sectional study was carried out from January 2021 to October 2022 and 149 participants were recruited after fulfilling the inclusion and exclusion criteria with approval from ethical board. Statistical analysis was done using SPSS statistics version 21.0 WINDOWS (IBM Corp. Armonk, NY, USA). Results: Among the 149 cases, 89 (59.7%) neonates were symptomatic and 60 (40%) neonates were asymptomatic. The most common presentation were poor feeding and plethora in 89 neonates each (59.7% each), followed by lethargy (39.6%), hypogycemia (30.2%), jaundice (29.5%), necrotizing enterocolitis (21.5%), cyanosis (10%) and oliguria (10%). Partial exchange therapy was done in 30 neonates (20%), 59 neonates (39.6%) required intravenous fluid and 60 neonates (40.3%) were treated conservatively. All neonates were successfully discharged and no deaths were noted in our study. Conclusions: Anticipation, early recognition and intervention can prevent acute short-term complications and long-term sequelae of this easy to treat disorder.

The Epidemiology and Clinical Burdens of Human Parainfluenza Virus Infections Amongst Hospitalized Children Under 5 Years of Age in Jordan: A National Multi-Center Cross-Sectional Study

Human parainfluenza virus (HPIV) is a major cause of respiratory illnesses in children under five years, with clinical manifestations ranging from mild upper respiratory tract infections to severe lower respiratory tract diseases. This multi-center, cross-sectional study investigated the burden, clinical features, and predictors of respiratory viral infections in hospitalized children across four sites in Jordan. Nasopharyngeal specimens from 1000 eligible children were analyzed. In this article, we focused on HPIV infections. The overall HPIV positivity rate was 22.6%, with HPIV-3 accounting for 90.3% of cases. Significant geographic variability was observed, with higher positivity rates in the southern region. HPIV-positive cases frequently presented with symptoms like nasal congestion, tachypnea, and poor feeding. Co-infections with respiratory syncytial virus (RSV) or influenza were associated with worse outcomes, including an increased need for invasive ventilation. The logistic regression identified male gender, asthma, and respiratory acidosis as predictors of complications. Geographic differences in HPIV prevalence and severity were notable, emphasizing the influence of environmental and socioeconomic factors. These findings underscore the urgent need for enhanced HPIV surveillance, targeted public health interventions, and vaccine development to mitigate the disease burden. This study provides critical insights that guide healthcare strategies and improve outcomes in young children at risk of severe HPIV infections.

Validation of the Caregiver Analysis of Reported Experiences with Swallowing Disorders (CARES) Screening Tool for Neurodegenerative Disease.

Swallowing difficulties have a substantial impact on the burden experienced by care partners of individuals with neurodegenerative disease. Given this, there is a clear need to easily identify and quantify the unique aspects of swallowing-related burden. The purpose of this study was to establish the validity and reliability of the Caregiver Analysis of Reported Experiences with Swallowing Disorders (CARES) screening tool in care partners of individuals with neurodegenerative disease. Survey data were collected from an international sample of 212 individuals caring for family members with amyotrophic lateral sclerosis (n = 49), dementia (n = 110), or Parkinson's disease (n = 53). Respondents completed the CARES, Eating Assessment Tool-10, International Dysphagia Diet Standardisation Initiative-Functional Diet Scale, and Zarit Burden Interview. Reliability and validity of the CARES were evaluated via internal consistency alpha coefficients, Spearman's rho correlations, and logistic regression analyses with receiver operating characteristic (ROC) curves. CARES scores demonstrated excellent internal consistency (α = .90-.95) and high test-retest reliability (r = .86-.91). The CARES was found to be valid, as increased swallowing-related burden was associated with increased severity of swallowing difficulties (r = .79 to .84), diet restrictiveness (r = -.50 to -.54), and general caregiver burden (r = .36 to .40). The CARES had excellent discrimination between care partners with and without self-reported swallowing-related burden, with a score of ≥ 4 suggesting a heightened risk of experiencing this burden. Results establish the CARES as a valid and reliable screening tool that can detect burden related to swallowing difficulties among care partners of individuals living with neurodegenerative disease (score ≥ 4). Clinical implementation of the CARES requires the concerted efforts of the larger multidisciplinary team who can collaboratively identify the presence of burden and target the multifaceted sources of burden that a care partner may be experiencing.

Co-occurrence of Phelan-McDermid syndrome and metachromatic leukodystrophy

Very few cases have been described so far with co-occurrence of Phelan-McDermid syndrome (PMS) and metachromatic leukodystrophy (MLD). Those patients harbour a chromosome (chr) 22q13deletion encompassing at least the SHANK3 and ARSA genes and a pathogenic variant in the arylsulfatase A (ARSA) gene residing on the other allele. The deletion in chr22q13 results in PMS phenotype and the presence of pathogenic variation on the other intact copy of ARSA gene, leads to MLD phenotype due to biallelic loss of ARSA function. We describe a male infant, born to a third-degree consanguineous couple, who exhibited neuroregression at the age of 8 months, presented with developmental delay, hypotonia which rapidly progressed to feeding difficulties, axial hypotonia, ptosis, sleep disturbance, dystonia, spasticity, and abnormal eye movements. Brain MRI showed T2 hyperintensities consistent with MLD. Biochemical workup showed deficiency of ARSA enzyme activity. Genetic investigations revealed heterozygous deletion of size 2.5 Mb on chr 22q13.3 encompassing the entire ARSA gene and a pathogenic variant in the other copy of ARSA gene. Parents and sibling were tested and informed about the disease management and genetic testing in extended family members to understand the risk and preventive measures. Few case reports have proposed screening for urine sulfatides levels at the time of PMS diagnosis to identify pre-symptomatic or asymptomatic MLD patients to facilitate management and our case supports this proposal.

Successful Management of Cyanosis Due to Tongue Fall Back of 17 Days Newborn with Cleft Palate: A Case Report

Background: Cleft Lip and Palate (CLP) are one of the most frequently occurring craniofacial congenital anomalies. Itimpairs an individual's aesthetics, speech, hearing, and psychological and social life. Respiratory difficulty and feeding problems are the primary concern of cleft palate newborns. Case Presentation: A 17-day-old newborn presented to the Neonatal Intensive Care Unit on 10 January 2023 with difficulty in respiration and causes nasal regurgitation. Then the patient was referred to dental OPD to place a palatal device/obturator. The case presented here discusses the management of breathing problems to halt cyanosis in a neonate with a cleft palate. Conclusion: Another immediate problem for a newborn with a cleft lip/palate is difficulty in feeding. After adjusting an obturator to the patient’s mouth, she recovered from cyanosis. Currently, she is pretty comfortable in respiration as well as feeding. Chatt Maa Shi Hosp Med Coll J; Vol.23 (1); January 2024; Page 104-107

Comprehensive Clinical and Genetic Characterization of a Spanish Cohort of 22 Patients With Bainbridge-Ropers Syndrome.

Bainbridge-Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the ASXL3 gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype-phenotype correlation. We identified 19 ASXL3 variants, nine of which are novel. We documented recurrence in nontwin siblings due to parental mosaicism. The predominant prenatal finding was intrauterine growth restriction (35%) followed, after birth, by feeding difficulties (90.5%), hypotonia (85.7%), and gastroesophageal reflux disease (82.4%). Later in life, intellectual disability, language impairment, autism spectrum disorder (75%), and joint laxity (73.7%) were noted. Individuals with variants in the 3' mutational cluster region (MCR) of exon 12 exhibited more perinatal feeding problems, and those with variants in the 5' MCR of exon 11 displayed lower percentiles in height and occipitofrontal circumference, as well as higher frequency of arched eyebrows. This study is the first characterization of a Spanish BRPS cohort, with more than 50 clinical features analyzed, representing the most detailed phenotypic analysis to date.

Left coronary ostial isolation in a young boy caused by a dysplastic aortic valve: a case report

Abstract Background Ischemic cardiac chest pain and coronary artery abnormalities are uncommon in children. The long-term implications of missed or delayed diagnosis are myocardial ischemia and risk of sudden cardiac death. Improvement in non-invasive imaging has made diagnosis and surgical planning possible with multi-modal imaging. Case summary A 12-year-old boy with ischemic chest pain caused by isolation of the left coronary ostium in the context of a dysplastic aortic valve. There was a delay to formal diagnosis. Surgical aortic valve repair resulted in complete resolution of symptoms. Ethics approved (SCHN: CCR2023/5). Discussion Isolation of the left coronary ostium caused by a dysplastic aortic valve (without supravalvar stenosis) is an example of a rare cause of ischemic chest pain in children. To our knowledge, only ten pediatric case reports are published in English. In reported cases, presenting features varied from poor feeding and a murmur in infants to chest pain, syncope or cardiac arrest in adolescents. Historically, angiography during a cardiac catheter procedure was required for diagnosis, however improvements in non-invasive imaging techniques have resulted in the diagnosis being possible on echocardiography (supported by CT angiography or cardiac MRI).

Parents’ views and experiences of raising babies born with cleft lip and palate: a qualitative study

BackgroundParents of children born with cleft lip/palate encounter numerous challenges. This study aims to provide a deeper understanding for authorities to better support these parents by exploring the views and experiences of Iranian parents raising babies with cleft lip/palate through qualitative research.MethodsThis qualitative study collected data through face-to-face, in-depth, semi-structured interviews. Using purposive sampling, parents of children with cleft lip/palate who visited the Department of Oral and Maxillofacial Surgery at the Children’s Medical Center in Tehran, Iran, were selected. Thematic content analysis was employed to interpret the data and identify themes and subthemes.ResultsFrom 20 interviews, six themes were identified. The diagnosis theme was associated with timing. Key concerns within the psychosocial experiences theme included initial reactions, pressure from society, the child’s future in the community, hiding from family, feeling guilty about the anomaly, and couples’ relationships. The challenges in childcare theme included feeding difficulties, financial challenges, and cleft treatments. The information acquisition theme included primary awareness and the importance of knowing how to care for the child. The coping theme included gaining awareness, accepting the problem as God’s will and destiny, minimizing the significance of the child’s cleft, and support. Parents had concerns about informing the child of his/her condition.ConclusionsParents of infants with cleft lip/palate feel unsupported by medical staff in feeding practices and seek improved training for staff. They propose a program to empower staff and advocate for psychological support for parents. Access to specialized baby bottles and financial support is crucial, along with establishing a parent-led community for sharing experiences.

Growth and development patterns of Noonan syndrome and advances in the treatment of short stature

Patients with Noonan syndrome (NS) are born with normal or slightly lower body length and weight compared to the normal ranges. However, their height gradually falls behind that of the general population, leading to growth retardation and delayed puberty. In China, the incidence of short stature in patients with NS is approximately 65%. Short stature in these patients arises from multiple causes, including feeding difficulties in infancy, comorbidities such as congenital heart disease, genetic heterogeneity, and disorders of the growth hormone/insulin-like growth factor-1 axis. Growth hormone is commonly used to alleviate symptoms of short stature. This article reviews the growth and development patterns at different stages of NS, analyzes the causes of short stature, and summarizes the latest advances in treatment to provide new insights for the diagnosis and management of short stature in patients with NS.

Histopathologic Marks of Tongue in a Mouse Model of Oculopharyngeal Muscular Dystrophy Suggest Biomechanical Defects.

The tongue facilitates vital activities such as swallowing. Difficulty swallowing (dysphagia) is common in the elderly population and in patients with adult-onset neuromuscular disease. In oculopharyngeal muscular dystrophy (OPMD), dysphagia is often the first symptom. OPMD is an autosomal-dominant myopathy caused by a trinucleotide-expansion mutation in the gene encoding nuclear poly(A)-binding protein (PABPN)-1. Expanded-mutant PABPN1 forms insoluble nuclear aggregates that reduce the levels of the soluble form. Clinical tongue involvement in OPMD has been documented but is poorly understood. Histopathologic analysis of the tongue in an OPMD mouse model was done by light and electron microscopy combined with RNA sequencing. PABPN1 nuclear aggregates were found at moderate levels, whereas deposition of insoluble PABPN1 in blood vessels was prominent already at age 4 months. Muscle wasting of the tongue was age associated. RNA signatures of the OPMD tongue were enriched for mitochondrial and cytoskeletal genes. Electron microscopy revealed abnormalities in sarcomere and mitochondria organization in A17/+ mice, suggesting an energy and contractile deficit in OPMD tongue. This detailed analysis of the histopathology of the tongue in the A17/+ mouse model opens new avenues for understanding the mechanisms of dysphagia.

Gastrostomy tube feeding in children: a single-center experience

BackgroundDespite the widespread use of percutaneous endoscopic gastrostomy (PEG) in pediatric populations, there is a paucity of data on the indications and outcomes of this procedure in Switzerland. This manuscript presents our experience with PEG indication, outcomes, and related complications in children.MethodsThis single-center retrospective study included patients < 18 years old who underwent PEG placement between 2007 and 2016. We retrieved demographics, PEG indications, associated comorbidities, pre-placement workup, growth parameters up to 12 months, and associated complications.ResultsEighty-one patients were included, with a median age of 7 years. Common indications included inadequate caloric intake (85%), failure to thrive, and feeding difficulties. Neurological conditions (46%) were the most commonly associated comorbidity. Thirty-six patients (44%) underwent a pH study before PEG placement. There were significant increases in z-scores for weight (p < 0.002) and body mass index (p < 0.001) 12 months after PEG placement. Minor complications were relatively frequent (n = 55, 68%), mainly granulation tissue or local erythema. Two patients had major complications.ConclusionPEG is a safe technique for providing long-term enteral nutrition in children, with neurological disease being the most common clinical indication. Our experience demonstrated significant weight gain in children after one year of PEG, with frequent but well-controlled complications.

Assessing neonatal nurses: transitioning preterm infants to oral feeding - a multicenter cross-sectional study

BackgroundIn Egypt, approximately 10% of preterm deliveries occur between 32 and fewer than 37 weeks, leading to high neonatal intensive care unit (NICU) admissions. Preterm infants often face oral feeding difficulties due to immature development, which can lead to extended hospital stays and increased health risks.AimTo assess neonatal nurses’ performance in terms of the transition to oral feeding in preterm infants, focusing on knowledge, practices, and attitudes.MethodsA descriptive, quantitative, multicenter, cross-sectional study was conducted across 16 hospitals in five governorates in Egypt from November 2023 to March 2024 involving 553 neonatal nurses. The data were collected through a self-administered questionnaire assessing knowledge and attitudes and through an observed checklist for nurses’ practices. The study used statistical methods, including binary logistic regression, to analyze the data.ResultsThe findings revealed significant knowledge gaps among nurses, particularly in terms of oro-motor function, suck-swallow-breathe patterns, and nonnutritive sucking. A total of 64.6% of the nurses had unsatisfactory knowledge, 58.6% had unsatisfactory practices, and 45% had a negative attitude toward the oral feeding transition. Key predictors of satisfactory practices included higher education levels, full-time employment, and positive attitudes.ConclusionThis study highlights critical gaps in neonatal nurses’ knowledge and practices regarding the transition to oral feeding in preterm infants. Addressing these gaps through targeted educational interventions and ongoing support is essential for improving care quality and outcomes for infants. The findings revealed that a substantial proportion of nurses lacked adequate knowledge of critical areas, such as oro-motor function, the suck-swallow-breathe pattern, and nonnutritive sucking. These knowledge deficits could hinder the ability of nurses to provide optimal care during this crucial transition.

Complementarity of biomarker screening and genetic analyses based on the case of an attenuated multiple sulfatase deficiency.

Multiple sulfatase deficiency (MSD) is an ultra-rare lysosomal disease caused by defective activation of cellular sulfatases comprising clinical features of mucopolysaccharidoses, sphingolipidoses, and other sulfatase deficiencies. We present a case of an infant with feeding difficulties related to autism spectrum disorder (ASD) who was diagnosed at 10months of age with MSD by next-generation sequencing (NGS). Biochemical results obtained in dried blood spot (DBS) samples were inconsistent and not suggesting MSD in the light of identified pathogenic SUMF1 variants. However, follow-up analyses at 20months of age revealed an increased concentration of sulfatides in DBS. It should be noted that biochemical tests, routinely used as screening methods, have a risk of false negative results, especially regarding mild/attenuated phenotypes, as presented in our report.

Lived experiences of dysphagia-related quality of life among esophageal cancer patients: a qualitative study

IntroductionEsophageal cancer impairs basic functions such as eating and drinking frequently resulting in difficulty swallowing (dysphagia) and other problems such as weight loss, pain, fatigue, and taste alterations. There is still a research gap in understanding the impact of dysphagia on quality of life, as patients continue to bear significant physical and psychological burdens despite advances in treatment. This study attempted to address this gap by examining the lived experiences of dysphagia-related quality of life among esophageal cancer patients.MethodsA phenomenological study was employed to analyze the data provided by 14 patients with esophageal cancer at the Oncology Center of the University of Gondar Comprehensive Specialized Hospital from March to April 2023. An interview guide was employed to carry out in-depth interviews with purposively selected patients. The interviews were audio-taped, translated, transcribed, and analysed using thematic analysis.ResultsThree main themes emerged from the analysis of the participant interviews: physical challenges related to difficulty swallowing, altered dietary habits, and struggle to maintain weight; psychosocial strain, including emotional distress and social isolation; and reliance on assistance, encompassing both dependency and financial burden.Conclusion and recommendationsThis study underscores the significant physical, emotional, and social challenges experienced by esophageal cancer patients with dysphagia. To enhance support, healthcare providers should develop personalized care plans that address both the physical and emotional aspects of dysphagia, with sensitivity to cultural practices. Efforts should also be made to alleviate feelings of dependency and promote public awareness to reduce stigma and build a more supportive community.

Exploring Dysphagia in Congenital Diaphragmatic Hernia: A Retrospective Analysis.

Background: Congenital diaphragmatic hernia (CDH) is a complex congenital disorder often accompanied by long-term feeding difficulties. There is a paucity of published data regarding the impact of swallowing difficulties on long-term patient outcomes. Our study attempts to evaluate this phenomenon. Methods: A retrospective chart review of infants born with CDH between 2021 and 2022 identified 45 patients. The following variables were identified: need for swallow study, stomach location, defect type, need for anti-reflux therapy, need for nasogastric tube (NG) or gastric tube (GT) at time of discharge, poor growth, and frequency of respiratory infections during the first 12 months of life. Results: Thirty-one percent of patients (n = 14) underwent a swallow study, 20% (n = 9) required long-term anti-reflux medications, 18% (n = 8) had a GT and 59% (n = 26) had an NG in place at time of discharge, 44% (n = 17) experienced poor growth as an outpatient, and 35% (n = 16) had respiratory infections in the first 12 months of life requiring hospitalization. Infants with a Type D defect commonly required GT at discharge (40%), experienced respiratory infections in the first 12 months (67%), and had poor growth as an outpatient (67%). Conclusions: Our findings underscore the need for routine dysphagia screening in CDH infants during NICU admission. Differences in outcomes based on defect type suggest that early identification and targeted interventions for feeding and swallowing issues may improve long-term growth and respiratory outcomes for CDH patients. Further studies are warranted to develop standardized dysphagia management guidelines for this population.

Histoire naturelle des allergies alimentaires non IgE-médiées

Non-IgE-mediated food allergies are adverse immune reactions to certain food allergens that are specific for a given individual, but do not involve specific serum IgE antibodies. They mainly affect infants and young children. They include allergic proctocolitis, food protein-induced enterocolis syndrome (FPIES), allergic enteropathy, aspecific digestive dysmotility (e.g., severe reflux, constipation) and certain eosinophilic oesophagitis (EoE) responding to the avoidance diet. The most common allergen involved is cow's milk, but other foods may be responsible, particularly in breast-fed infants, although this is rare. The main symptoms are haematochezia in allergic proctocolitis, acute vomiting with pallor and hypotonia in FPIES, stunted growth and chronic diarrhoea in allergic enteropathy, and reflux with feeding difficulties in infantile EoE. Eviction-reintroduction of the suspected allergen is used as a diagnostic test in allergic proctocolitis and enteropathy. In FPIES, there is a clinical definition. For EoE, histological analysis of oesophageal biopsies makes the diagnosis after elimination of differential diagnoses. Treatment involves avoiding the allergen responsible until tolerance is acquired. With the exception of EoE, the course of the disease is favourable in the first 2–3 years of life. There is a risk of developing functional intestinal disorders and atopic diseases. EoE is a chronic disease, with possible cases of remission in paediatrics. The main complications are oesophageal stenosis, food impaction and oesophageal perforation.

Longitudinal Outcomes in Noonan Syndrome

Longitudinal Outcomes in Noonan Syndrome

Stuve‐wiedemann syndrome and cornea consequences: A rare case report

Aims/Purpose: Stuve‐Wiedemann Syndrome (STWS) is a rare genetic disorder inherited in an autosomal recessive manner. The condition leads to respiratory and feeding difficulties, as well as episodes of hyperthermia, typically resulting in death within the first two years of life. It is characterized by bone dysplasia, hypotonia, and dysautonomia, accompanied by ocular and neuropathic features. The absence of corneal reflexes, decreased blink reflexes, and corneal opacities are recognized markers. Here, we report a case of STWS with corneal hypoesthesia and opacity, highlighting the current challenges in management and treatment.Methods: A 16‐year‐old male was admitted to the Ophthalmology Department of the University of São Paulo in 2010 due to a history of multiple corneal ulcer episodes. At the slip lamp examination, he presented leukoma formation and corneal hypoesthesia. The patient also presented several orthopedic alterations. After a multidisciplinary investigation, the diagnosis of STWS was made, and follow‐up was conducted. He has been treated with lubricating eye drops and ointment for the last few years. Since 2014, he has not experienced corneal ulcers. At his last appointment in 2024, he kept corneal exposure due to decreased blink reflexes, leukomas in both eyes, mild superficial punctate keratitis and complained of dry eye and eye itching despite the treatment. Therefore, a tarsoconjunctival flap was indicated as a surgical method, having been employed due to persistent corneal involvement.Results: The case's challenges relate to the management and treatment of corneal involvement in patients with STWS, as most often, they are children who don’t express discomfort or show symptoms due to the characteristic neuropathy of their lesions. Additionally, it's essential to reduce corneal exposure and its consequences.Conclusions: Although rare, ophthalmologists must be aware of this ocular involvement in STWS for early diagnosis and appropriate management.References Hernández‐García S et al. Neuroparalytic keratopathy in Stüve‐Wiedemann syndrome treated with tarsoconjunctival flap. Indian J Ophthalmol. 2023

Outpatient Infant Botulism in the United States, 1976-2021

To characterize cases of outpatients with infant botulism (IB) in the US identified by the Infant Botulism Treatment and Prevention Program at the California Department of Public Health from 1976 through2021. Outpatient IB cases were defined as patients presenting with an illness consistent with the known paralyzing action of botulinum neurotoxin and with laboratory confirmation. Outpatient cases were distinguished from the majority of patients with IB by the atypical fact that they did not require hospitalization throughout the course of their illness. Of the 4372 cases of IB identified by the Infant Botulism Treatment and Prevention Program over a 45-year period (1976-2021), 17 (0.4%) were outpatient cases. Most (11/17; 65%) cases occurred in California. The median age at disease onset was 20weeks (range=6 to 55weeks). The most common symptom among cases was constipation (16/17; 94%). Most patients (16/17; 94%) had at least one cranial nerve palsy, manifested as decreased head control, ptosis, weak cry, or poor suck. Outpatient IB occurs nationwide, although clinical diagnosis may be difficult because the severity of symptoms do not necessitate hospitalization or more comprehensive clinical intervention. Identification of outpatient cases requires an astute clinician and a capable, willing diagnostic testing laboratory. It is likely that more outpatient cases of IB are occurring than are presently recognized in infants mildly affected by this disease. Healthcare providers should consider the possibility of IB when presented with a previously well infant with failure to thrive, poor feeding, constipation, mild hypotonia, or cranial nerve palsy.

Enhanced oral absorption and biodistribution to submandibular salivary glands of D-limonene in Sprague Dawley rats via a liquid-lipid formulation approach.

Decreased saliva production due to salivary gland damage can result in difficulty speaking and swallowing, significantly reducing quality of life for head and neck cancer patients receiving radiotherapy. It is therefore imperative that treatment options are available to mitigate the effects of these debilitating side effects. D-limonene, a naturally occurring terpene, has shown protective effects on saliva production during radiotherapy treatment of mice, however the lipophilic nature of the molecule has necessitated a high oral dose to facilitate sufficient absorption. In this study, lipid-based drug delivery systems have been utilised to formulate D-limonene in order to reduce undesirable gastrointestinal side effects and increase solubility for enhanced absorption. Lipid-based formulations produced up to 180-fold increased solubility over pure D-limonene, coupled with enhanced storage stability and protection against oxidation. Furthermore, pharmacokinetic evaluation of optimised lipid-based formulations in Sprague Dawley rats displayed up to a 51.25-fold increase in bioavailability relative to pure oral D-limonene. Finally, elevated levels of lipid-formulated D-limonene were localised within the submandibular salivary glands, indicating potential for local action on saliva production. Overall, the administration of D-limonene utilising lipid-based formulations shows significant promise for advancing prevention and treatment strategies for xerostomia.