Oral Microbiota of Infants in Maternal Gestational Diabetes: A Systematic Review.

Gestational diabetes mellitus (GDM) affects approximately 5-20% of pregnant women and is associated with adverse pregnancy outcomes. This review aimed to assess whether the oral microbiota of infants and their mothers with GDM had a different composition from that found in unaffected women and offspring. PubMed, Embase, Scopus, and Google Scholar were searched in December 2023 after protocol registration in the International Prospective Register of Systematic Reviews (CRD42023406505). Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. Overall, 1113 articles were identified; after evaluating the full texts, 12 papers were included in the qualitative analysis. In six studies of the eight included, significant differences in microbiota between M-GDM and M-nGDM were found. In four studies, a depletion of Firmicutes and an enrichment of Proteobacteria was found in the microbiota of infants. Since all included studies were judged to have high risk of bias, a quantitative synthesis of the results was not carried out. In conclusion, although the oral microbiota of infants from mothers with GDM could be different from that of infants from mothers without GDM, there is insufficient evidence to clarify this aspect so far.

Is Italian Dentists' Knowledge of Enamel Development Defects Adequate? A Nationwide Survey.

OBJECTIVES: Correct identification and management of Developmental Defects of Enamel (DDEs) are essential to provide the best possible treatment. The present survey aims to investigate Italian dentists' knowledge of DDEs, their ability to recognise the different clinical pictures, and to choose the most appropriate clinical approach. METHODS: A cross-sectional survey was planned based on a questionnaire including 27 closed-ended questions, and that proposed 4 clinical pictures, molar incisor hypomineralisation (MIH), amelogenesis imperfecta (AI), dental fluorosis (DF), and an initial caries lesion (ICL). It was distributed by e-mail to all Italian dentists (N = 63,883) through the Italian Federation of Doctors and Dentists. Discrete variables were expressed as absolute and relative frequencies (%). A multivariate analysis assessed whether socio-demographic variables correlated with the answers' truthfulness. RESULTS: About 5017 questionnaires were included and analysed. Although 90.19% of the sample stated that they had received information on DDEs, a significant percentage did not recognise MIH (36.36%), AI (48.34%), DF (71.50%), and ICL (46.62%). Only 57.07% correctly classified enamel hypomineralisation as a qualitative defect, and even fewer, 54.45%, classified enamel hypoplasia as a quantitative defect. According to the logistic regressions, female dentists, dentists who treat mainly children and received information about DDEs, were more likely to recognise the 4 clinical pictures (P < .01). CONCLUSIONS: Italian dentists showed many knowledge gaps on DDEs that need to be filled; those who received formal training were more capable of correctly identifying the defects and were more likely to prescribe an appropriate management approach for the defects. CLINICAL SIGNIFICANCE: Increasing university courses and continuing education on diagnosing and managing DDEs seems reasonable to fill the knowledge gap on DDEs.

Effects of Hydroxyapatite-Containing Toothpastes on Some Caries-Related Variables: A Randomised Clinical Trial.

OBJECTIVES: This randomised clinical trial was designed and carried out with the aim to evaluate the capacity of fluoride-substituted hydroxyapatite (HAF) toothpaste to modulate oral microflora composition and biofilm acidogenicity in schoolchildren. METHODS: In all, 610 children (4 to 5 and 6 to 7 years) were enrolled. Four toothpastes were randomly administered during 24 months: 2 contained fluoride-substituted hydroxyapatite (HAF1000 and HAF1450; 1000 and 1450 ppmF) and magnesium-, strontium-, and carbonate-substituted hydroxyapatite in a chitosan matrix, and 2 were monofluorophosphate fluoridated toothpastes (F1000 and F1450; 1000 and 1450 ppmF). Caries lesions were assessed by International Caries Detection and Assessment System scores, supragingival plaque was sampled from the approximal sites between primary molars using sterile Gracey curettes for microbiological analysis, and plaque pH curves after sucrose challenge were assessed at baseline and reevaluated after 1 year and after 2 years. The minimum and maximum pH decrease was calculated for caries-free patients and participants with a caries lesion(s) at baseline and at the end of the experimental period (24 months). Differences amongst measurements were analysed with 1-way analysis of variance. RESULTS: During the trial, the minimum pH value increased statistically significantly in all groups; in HAF1000 and HAF1450, the increase was greatest. At the end of trial, in the 2 HAF groups all primary cariogenic bacteria were statistically significantly lower with respect to F groups (P = .03 for Streptococcus mutans and sobrinus, for Lactobacillus casei, and for Lactobacillus fermentum). CONCLUSIONS: The trial provides robust but still inconclusive evidence on the efficacy of HAF toothpastes compared to traditional fluoridated toothpastes to reduce caries risk factors and to prevent caries lesions.

Distribution of initial caries lesions in relation to fixed orthodontic therapy. A systematic review and meta-analysis.

BACKGROUND: Initial caries lesion (ICLs) adjacent to orthodontic brackets are the most common side effect of orthodontic treatment with fixed appliances. The reported prevalence is uncertain and varies considerably across studies, from 27% to 97%. OBJECTIVES: This paper was designed to evaluate and synthesize the available evidence on the prevalence and incidence rates of ICLs in relation to orthodontic treatment. Selection criteria: The review (Prospero protocol CRD42023412952) included randomized and non-randomized clinical trials of interventions, cohort studies, and cross-sectional studies, published after 1990 on the prevalence or incidence of ICLs during or after orthodontic treatment with fixed appliances. Search methods: Pubmed, Scopus, and Embase databases were searched from 1990 until 01 May 2023. The risk of bias assessment was performed with RoB 2 and ROBINS-I tool and the Joanna Briggs Institute Critical Appraisal Checklist. Data collection and analysis: The proportion of individuals with ICLs, reported as the number/percentage of individuals/teeth with ICLs or mean number of ICLs per subject, were used to synthesize results. RESULTS: The search yielded a total of 468 papers; 21 studies were included in the systematic review, 2 of which were not included in the meta-analysis. The prevalence rate [95%CI] of ICLs was 0.57% [0.48; 0.65] in 1448 patients, 0.22% [0.14; 0.33] in 11583 teeth, with a mean number of lesions equal to 2.24 [1.79; 2.70] in 484 patients evaluated. The incidence rate of new carious lesions developed during orthodontic treatment was 0.48% [0.33; 0.63] in 533 patients, 0.15% [0.08; 0.26] in 1890 teeth with a mean number of ICLs equal to 2.29 [1.12; 3.46] in 208 patients evaluated. LIMITATIONS: Although the high number of included studies and the overall good quality, there was a significant heterogeneity in the collected data. CONCLUSION: The prevalence and incidence rates of ICLs in subjects undergoing orthodontic treatment are quite high and raise some concerns in terms of risk assessment of orthodontic treatment. ICLs represent an alarming challenge for both patients and professionals. Effective caries prevention strategies during treatment need to be considered and implemented where appropriate.

Knowledge and attitudes on oral health of women during pregnancy and their children: an online survey.

BACKGROUND: Life-long healthy behaviors are established during pregnancy and the first years of life. In this cross-sectional survey, new mothers with a high level of schooling living in Northern Italy (Lombardy Region) were interviewed to assess their knowledge and attitudes towards their and child oral health. METHODS: A questionnaire (27 items) was developed to assess socio-demographic factors, knowledge, and attitudes towards maternal and child oral health. The questionnaire was disseminated in perinatal courses, private gynecological clinics, and via social media. Mothers aged ≥18 years, with at least a child aged 0-36 months, with a high school diploma or higher, were included in the survey. RESULTS: A total of 1340 women completed the questionnaire, 1297 of whom had a child aged 0-36 months, 792 lived in Lombardy, and 600 had a high level of education and were finally included. About half of the sample (44.67%) was aged between 31 and 35 years, 76.50% were employed, and the majority had only one child (81.50%). During pregnancy, 28.33% of the sample reported problems with teeth and gums, while only 36.00% visited a dentist. More than 40% of the sample said they were not aware of a possible link between oral health and pregnancy, and 73.17% had not received any advice about their oral health or the future health of their baby's mouth. Less than 20% of women were aware of the increased caries risk associated with prolonged or night-time breastfeeding. Better knowledge/attitude was associated with the age of the child (p < 0.05), the number of children (p < 0.05) and whether the mother had received advice during pregnancy (p < 0.05). CONCLUSIONS: The results of this survey show a lack of dental care during pregnancy, a lack of information about oral health from health professionals during and after pregnancy, and consequently gaps in the knowledge needed to care for the oral health of the woman and her child. There is a need for training in oral health for pregnant women and new mothers, but also a need for behavioural change among health professionals who care for pregnant women.

Conscious Sedation for Dental Treatments in Subjects with Intellectual Disability: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis was aimed to investigate the conscious sedation efficiency in patients with intellectual disability undergoing dental treatment (PROSPERO CRD42022344292). Four scientific databases were searched by ad-hoc prepared strings. The literature search yielded 731 papers: 426 were selected, 42 were obtained in full-text format, and 4 more were added after hand searching. Fourteen studies were finally included, 11 of which were included in the meta-analysis (random effect model). A high heterogeneity in the drugs used and route of administration was retrieved. Success rate, occurrence of side effects, and deep sedation occurrence were combined to give an overall efficiency of each drug. N2O/O2 reported the highest efficiency (effect size = 0.90; p < 0.01) and proved to be more efficient when used alone. Nine papers reported a success rate of sedation of 80% or more. The prevalence of side effects (6 studies) ranged from 3% to 40%. Enteral and parenteral benzodiazepines showed the same overall efficiency (effect size = 0.86). No meta-analysis has yet been conducted to define the most effective and safest way to achieve conscious sedation in patients with intellectual disability; nitrous oxide appears to be the best choice to perform conscious sedation in patients with intellectual disability undergoing dental treatment.

Dental and Dental Hygiene Students' Knowledge and Capacity to Discriminate the Developmental Defects of Enamel: A Self-Submitted Questionnaire Survey.

Background: A prompt and accurate diagnosis of developmental defects of enamel (DDE) is mandatory for proper treatment management. This cross-sectional survey, designed and carried out using anonymous self-administered questionnaires, aimed to assess dental and dental hygiene students' knowledge and their capability to identify different enamel development defects. Methods: The questionnaire consisted of twenty-eight closed-ended questions. Two different samples of undergraduate students were selected and enrolled: a group of dental hygiene (GDH) students and a group of dental (GD) students. A multivariate logistic regression was performed by adopting the correct answers as explanatory variables to assess the difference between the two groups. Results: Overall, 301 completed questionnaires were analyzed: 157 from the GDH and 144 from the GD. The dental student group showed better knowledge than the GDH of enamel hypomineralization and hypoplasia (p = 0.03 for both). A quarter (25.25%) of the total sample correctly identified the period of development of dental fluorosis with a statistically significant difference between the groups (p < 0.01). Amelogenesis imperfecta (AI) was identified as a genetic disease by 64.45% of the sample, with a better performance from the GD (p = 0.01), while no statistical differences were found between the groups regarding molar incisor hypomineralization. Multivariate analysis showed that AI (OR = 0.40, [0.23;0.69], p < 0.01) and caries lesion (OR = 0.58, [0.34;0.94], p = 0.03) were better recognized by the GD. Conclusions: Disparities exist in the knowledge and management of DDE among dental and dental hygiene students in Italy; however, significant knowledge gaps were found in both groups. Education on the diagnosis and treatment of DDE during the training for dental and dental hygiene students needs to be strongly implemented.

Silver Diamine Fluoride (SDF) Efficacy in Arresting Cavitated Caries Lesions in Primary Molars: A Systematic Review and Metanalysis.

A systematic review and meta-analysis were carried out to evaluate the efficacy of silver diamine fluoride (SDF) in controlling caries progression in cavitated primary molars. A search for randomized and non-randomized trials with follow-up > 6 months was performed using PubMed, Scopus and Embase. The Cochrane risk of bias tools were used for the quality assessment. The success rate and odds ratios were chosen to calculate the effect size for the meta-analysis. A total of 792 papers were identified and 9 were selected. A high variability regarding SDF application protocol was found; otherwise, caries arrest was always recorded using visual/tactile methods. Two studies were judged at low risk of bias, six at moderate risk and one at high risk. Data from five studies were aggregated for meta-analysis. Heterogeneity was found moderate (I2 = 35.69%, p = 0.18). SDF application was found to be overall effective (fixed effect model) in arresting caries progression (ES = 0.35, p < 0.01). In a total of 622 arrested lesions, out of 1205 considered, the caries arrest rate was 51.62% ± 27.40% (Confidence = 1.55) using SDF ≥ 38% applied annually or biannually. In conclusion, when applied to active cavitated caries lesions in primary molars, SDF appears to be effective in arresting dental caries progression, especially if applied biannually.

COVID-19 Pandemic and Remote Consultations in Children: A Bibliometric Analysis.

Telemedicine is becoming a standard method of consultation, and the COVID-19 pandemic has increased its need. Telemedicine is suitable for non-communicable diseases (NCDs) in the pediatric population, as these are chronic conditions that affect many children worldwide. The aim of this study was to analyze the bibliometric parameters of publications on the use of telemedicine for the most common NCDs in children before and after the COVID-19 pandemic. Following the electronic search, 585 records were selected. "Metabolic diseases" was the most frequent topic before and after the pandemic, accounting for 34.76% in 2017-2019 and 33.97% in 2020-2022. The average IF of the journals from which records were retrieved was 5.46 ± 4.62 before and 4.58 ± 2.82 after the pandemic, with no significant variation. The number of citations per reference averaged 14.71 ± 17.16 in 2017-2019 (95% CI: 12.07; 17.36) and 5.54 ± 13.71 in 2020-2022 (95% CI: 4.23; 6.86). Asthma, metabolic diseases, and neurodevelopmental disorders were the most explored topics. A relevant finding concerns the increasing number of observational studies after the pandemic, with a reduction of the interventional studies. The latter type of study should be recommended as it can increase the evaluation of new strategies for the management of NCDs.

Long-term caries prevention of dental sealants and fluoride varnish in children with autism spectrum disorders: a retrospective cohort study.

The aim was to compare two strategies for caries prevention in children with Autism Spectrum Disorders (ASDs). Participants were retrospectively retrieved and divided in two groups. Group one had first permanent molars treated with fluoride varnishes, FA group (n = 92, 9.43 ± 2.44 years) whilst the second, with dental sealant plus fluoride varnishes, FA + S group (n = 140, 7.77 ± 2.57 years). Logistic and multivariate analysis were run to evaluate the caries incidence, the retention rate of sealants, and background factors associated with caries risk over a period of at least 11 years. Survival rates from dental caries were statistically significantly higher in the FA + S group compared to the FA group (LogRank test p < 0.01). Dental sealant plus fluoride varnish played as a protective factor towards the development of caries (HR = 0.25 95%CI = 0.00/0.55 and HR = 0.34 95%CI = 0.00/0.66 in the upper right and left first molars; HR = 0.32 95%CI = 0.00/0.66 and HR = 0.26 95%CI = 0.00/0.58 in the lower right and left first molars). Dental sealants retention rate was high, ranging between 58.02% and 64.29%. No baseline variable was statistically significantly associated to the risk of caries development. Combined dental sealant and fluoride varnish application was more effective in reducing caries risk in first permanent molars of ASDs children than fluoride varnish alone. This preventive strategy should be therefore routinely applied in high caries risk patients as ASDs children.

Use of Visual Pedagogy to Help Children with ASDs Facing the First Dental Examination: A Randomized Controlled Trial.

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders that don't have a direct effect on oral health, but severe difficulties in oral hygiene and dental procedures expose people with ASDs to an increased risk of oral diseases. This RCT aimed to evaluate which pedagogical tool was the best to prepare children with ASDs for their first dental examination, either video or photo aids. Two different criteria were used to evaluate their efficacy: the achieved steps into which the procedure was divided (n = 8), and the level of cooperation according to the Frankl Behavioral Scale. One hundred-thirteen subjects were randomly assigned to the two groups and 84 subjects completed the trial (Video group n = 41; Photo group n = 43). A predictive model for the achievement of the Preliminary (1-4) or Dental (4-8) steps was performed using a multivariate logistic regression procedure. Children in the Video group achieved more steps, but the comparison between groups was statistically significant only for the Preliminary steps (p = 0.04). The percentage of subjects judged as cooperating was similar in the two groups. The results of this study underline that behavioural intervention should be used as an effective strategy to prepare subjects with ASDs for a dental examination.

Efficacy of HAF toothpastes in primary and permanent dentitions. A 2-years triple-blind RCT.

OBJECTIVES: The aim of this RCT was to compare the caries preventive efficacy and the slowing down of previous caries lesions of toothpastes containing fluoride biomimetic hydroxyapatite (HA) complex compared to sodium monofluorophosphate fluoridated toothpastes in Italian schoolchildren. To validate this hypothesis a triple-blind randomized clinical trial was designed. METHODS: In total 610 children (4-5 and 6-7 years) were enrolled. Four toothpastes, two containing fluoride-substituted hydroxyapatite (HAF) (1000 and 1450 ppmF) and magnesium-, strontium-, carbonate-substituted hydroxyapatite, in a chitosan matrix and two Mono fluoridated toothpastes (1000 and 1450 ppmF) were randomly administered during 24 months to two groups with younger children (Gyoung) and to two groups with older children (Gold), those containing 1450 ppmF. ICDAS was used to score lesions as initial (up to score 2), moderate (scores 3-4) and severe (scores 5-6). The children were instructed to brush for two minutes three times/day. Caries examination was repeated at 12 and 24 months. The efficacy of the treatment was assessed by calculating the reduction in Risk Ratio (RR) and the number needed to treat (NNT). Results; Overall, 518 patients (Gyoung = 268; Gold = 250) concluded the trial. The drop-rate was 11.84% for Gyoung and 17.22% for Gold. The caries increment at 24-month evaluation was statistically lower in the primary dentition in the HAF arms compared to the traditional fluoridated arms (0.18 vs 0.27 p = 0.04 in Gyoung and 0.16 vs 0.30 p = 0.01 in Gold for severe lesions). In the permanent dentition (Gold), caries increase was also statistically lower in the HAF arm, both for initial and severe lesions (0.09 vs 0.17 p = 0.02 and 0.18 vs 0.28 p = 0.01, respectively). In primary dentition, children receiving HAF Toothpaste had a RR of 39% (Gyoung) and 38% (Gold), compared to children receiving traditional Toothpastes. The RR in the permanent dentition was 29% in children treated with HAF toothpaste. Conclusions; The use of toothpastes containing biomimetic hydroxyapatite and fluoride reduces caries increment in children over a period of 2 years more than traditional fluoridated toothpastes.

Is Pediatric Dentistry a Topic of Interest for Pediatric Journals? A Scoping Review.

BACKGROUND: Pediatric dentistry shares many skills with pediatrics. This review evaluates the amount of literature on pediatric dentistry in the first 30 pediatric journals classified by the Web of Science in 2019. The aim was to perform a quantitative analysis of the main dental topics addressed. METHODS: A scoping review with the PRISMA-ScR criteria was performed. The Clarivate Analytics Journal Citation Report was consulted for journals ranked in the category "Pediatrics" in 2019. Papers were searched in PubMed using an ad hoc prepared string. RESULTS: A total of 504 papers were included. Papers on dental hard tissues were the most prevalent (45.6%), followed by dental public health (23.2%), orofacial development (15.3%), soft tissues related conditions (12.3%), and orofacial trauma (3.6%). Increasing trends have been observed for total papers published (R2 = 0.9822) and total dental papers (R2 = 0.8862), with no statistically significant differences (χ2(6) = 0.051 p > 0.05). The majority of papers (n = 292, 57.9%) were cited between 1 and 10 times, whilst less than 7% of papers received more than 40 citations. DISCUSSION: It is desirable that papers on pediatric dentistry increase in the pediatric scenario, allowing the two related disciplines to intertwine more in the future.

Is Visual Pedagogy Effective in Improving Cooperation Towards Oral Hygiene and Dental Care in Children with Autism Spectrum Disorder? A Systematic Review and Meta-Analysis.

Visual pedagogy has emerged as a new approach in improving dental care in children with autism spectrum disorders (ASDs). This paper aimed to evaluate and assess the scientific evidence on the use of visual pedagogy in improving oral hygiene skills and cooperation during dental care in children with ASDs. The review protocol was registered on the PROSPERO Register (CRD42020183030). Prospective clinical studies, randomized trials, interruptive case series, before and after comparison studies, and cross-sectional studies following the PRISMA guideline were searched in PubMed, Embase, Scopus, and Google Scholar using ad hoc prepared search strings. The search identified 379 papers, of which 342 were excluded after title and abstract evaluation, and 37 full-text papers were analyzed. An additional four papers were added after consulting reference lists. Eighteen papers were disregarded; 23 were finally included, and their potential bias was assessed using ROB-2 and ROBINS-I tools. The wide heterogenicity of the studies included does not allow for conclusive evidence on the effectiveness of visual pedagogy in oral hygiene skills and dental care. Nevertheless, a significant and unilateral tendency of the overall outcomes was found, suggesting that visual pedagogy supports ASD children in improving both oral hygiene skills and cooperation during dental care.

Rare Genetic Syndromes and Oral Anomalies: A Review of the Literature and Case Series with a New Classification Proposal.

Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district. So far, no classification of oral abnormalities in rare genetic syndromes is present in the literature. The aim of this narrative review is to analyze literature on rare genetic syndromes affecting dento-oro-maxillofacial structures (teeth, maxillary bones, oral soft tissues, or mixed) and to propose a classification according to the detected oral abnormalities. In addition, five significant cases of rare genetic syndromes are presented. The Scale for the Assessment of Narrative Review Articles (SANRA) was followed for this review. From 674 papers obtained through PubMed search, 351 were selected. Sixty-two rare genetic syndromes involving oral manifestations were found and classified. The proposed classification aims to help the clinician to easily understand which dento-oro-maxillofacial findings might be expected in the presence of each rare genetic syndrome. This immediate framework may both help in the diagnosis of dento-oro-maxillofacial anomalies related to the underlying pathology as well as facilitate the drafting of treatment plans with the involvement of a multidisciplinary team.

The Effect of Dental Treatment under General Anesthesia on Quality of Life and Growth and Blood Chemistry Parameters in Uncooperative Pediatric Patients with Compromised Oral Health: A Pilot Study.

BACKGROUND: The effect of untreated dental caries and their treatment under general anesthesia (GA) on the quality of life, growth, and blood chemistry parameters in uncooperative pediatric patients has not been extensively elucidated. The aims are to evaluate the impact of dental treatment under GA on oral health-related quality of life (OHRQoL) in uncooperative pediatric patients with severe dental caries and to assess the effect of dental treatment under GA on children's weight (Wt), height (Ht), Body Mass Index (BMI), and blood chemistry parameters. METHODS: Forty-three uncooperative children aged 3-14 years were selected. OHRQoL, through ECOHIS (Early Childhood Oral Health Impact Scale) and COHRQoL (Child Oral Health-Related Quality of Life) questionnaires, Wt, Ht, BMI, and blood chemistry parameters were measured at baseline and eight months after dental treatment under GA. RESULTS: At follow up, the reductions in the ECHOIS and the COHRQoL components were statistically significant (p < 0.0001), there was significant improvement in the anthropometric measures: 76.5% of children increased the percentile curves for weight, 68.6% for height, and 51.4% for BMI; for the blood chemistry parameters: ferritin improved in 68.6% of the samples, PCR in 65.7%, ESR in 68.6%, Vitamin D in 68.6%, and IGF-1 in 65.7%. CONCLUSIONS: Oral health status significantly influences OHRQoL, growth, and blood chemistry parameters in uncooperative pediatric patients.

Novel gel-like microemulsion for topical delivery of Amphotericin B / Una nueva microemulsión tipo gel para la aplicación tópica de anfotericina B

The aim of the present work was to develop a ME for topical delivery of Amphotericin B (AmB). Microemulsions (MEs) are versatile systems to solubilize drugs due to the presence of both a hydrophobic and a hydrophilic region, as well as a distinctive interface composed of surfactant and cosurfactant. MEs have been reported for many advantages for topical application of drugs. Considering that AmB has very low water solubility a screening of surfactants and oils was performed. A gel-like ME system, that can be applied topically without the need for thickeners agents, was selected. AmB was incorporated up to 1 mg/g and remained stable for at least 90 days both at 4 °C and room temperature, so this formulation would be appropriate as a compounding medication. An in vitro skin penetration test was performed, the applied dose penetrated (10.16 +/- 0.01 µg/cm²/h as estimated flux) and remained completely within the skin during the assay; AmB was not detected in the receptor compartment. In vitro antifungal and antileishmanial activity was tested and drug showed proper activity. AmB is a second line drug for the treatment of cutaneous leishmaniasis, but topical dosage forms are still lacking. This system is potentially useful for the treatment of skin infections avoiding drug toxic systemic effects.

Se desarrolló una microemulsión (ME) para la aplicación tópica de anfotericina B (AmB). Las ME son sistemas versátiles que facilitan la solubilización de principios activos y, además, presentan muchas ventajas para aplicar fármacos en forma tópica. La AmB posee muy baja solubilidad en agua, por lo cual se realizó una evaluación de su solubilidad en distintos aceites y surfactantes. Se confeccionaron diagramas ternarios de fase y se seleccionó una ME-gel que puede ser aplicada tópicamente sin el agregado de agentes espesantes. Se solubilizó hasta 1 mg/g de AmB y el fármaco permaneció estable durante al menos 90 días a 4 °C y a temperatura ambiente, por lo cual esta formulación sería apropiada como un medicamento magistral. El estudio in vitro de permeación en piel mostró que la dosis aplicada penetró completamente (flujo estimado de difusión 10,16 +/- 0,01 µg/cm²/h) y permaneció retenida en la misma durante el tiempo de estudio sin detectarse AmB en el compartimento receptor. La actividad antifúngica y antileishmania in vitro fue adecuada. La AmB es una droga de segunda línea en el tratamiento de la leishmaniasis cutánea; sin embargo, no se dispone de preparados para uso tópico. Esta formulación sería útil para el tratamiento local de las infecciones de piel, evitando efectos adversos sistémicos.

Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

Lipid-based microtubes for topical delivery of amphotericin B.

The self-assembly process is a valuable tool for constructing nano and microstructures. Microtubes (MTs) self-assembled from amphiphiles are novel promising nanomaterials as they have easy self-assembly in aqueous solutions, reproducibility and biocompatibility. The incorporation of amphotericin B (AmB) into lipid microtubes formed from 12-hydroxystearic acid (12HSA) when mixed with ethanolamine in aqueous media was investigated. MTs of several concentrations of lipid material and AmB were prepared. The structure was characterized by phase-contrast microscopy, TEM and SEM. The type of interaction was analyzed by FTIR and DSC. Stability studies were carried out at room temperature and at 4 °C. Loading efficiency of the system was found to be much higher than the drug solubility in water. MTs with 1% of 12HSA and 1 mg/ml of AmB showed to be the most stable formulation. In vitro skin penetration assay showed a flux of 18.20±3.35 µg/cm(2). Amb-loaded MTs in vitro antifungal activity was evaluated and formulation showed similar results to that of AmB deoxycholate showing that AmB retained its antifungal activity in the MTs formulation.

Solubility of amphotericin B in water-lecithin-dispersions and lecithin-based submicron emulsions.

The aim of this work was to evaluate water-lecithin-dispersions (WLDs) as carriers for amphotericin B (AmB) and to compare the drug solubility in WLDs and O/W lecithin-based submicron emulsions (SMEs) in order to evaluate the influence of lecithin content on the dosage form solubilization of the active compound. WLDs and different SMEs with either 1.2 or 2.4% of lecithin were prepared. WLD with 2.4% lecithin show a 10-fold increase in solubilization of AmB compared with 1.2% lecithin WLD. SMEs with 1.2% lecithin show an increase of over 400 times in solubilization compared with WLD containing the same concentration of lecithin, whereas SMEs with 2.4% lecithin show an increase of over 40 times compared with the corresponding WLD. Drug solubilization in SMEs with 2.4% lecithin is not significantly greater than in those containing 1.2% lecithin. The content of surfactant Brij 97 ® had a significant influence on drug solubilization in SMEs (P < 0.05). Results indicate that indicate that SMEs are proper systems to solubilize AmB. It can be assumed that solubilization is due to the formulation microstructure and not to the separate components themselves.