Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Intranasal drug delivery devices are a potential contamination source of airways / Dispositivos intranasais de medicamentos são uma potencial fonte de contaminação das vias aéreas

Background: The use of intranasal drug delivery devices (IDDD) for the treatment of allergic rhinitis (AR) is frequent because they are simple, efficient, and safe, and mainly because they are perceived as low-risk. However, it is speculated that contact between the nasal mucosa and an IDDD may give rise to infections once the nose is colonized by bacteria, and there are currently no proper instructions for IDDD sanitization. The objective of this study was to evaluate the possibility of contamination of an IDDD for topical medication after simulating use in healthy individuals. Methods: The in vitro study consisted of 14 healthy individuals of both sexes, between the ages of 18 and 24 years. Samples were collected immediately after the opening of each IDDD and after simulating use by the subjects. Afterwards, the samples were deposited in tubes and kept in an incubator at 37 °C. After 48 hours, the samples were inoculated on Müller-Hinton agar. Qualitative analyses of the appearance of the samples were performed after 24 and 48 hours, and after 72 hours the presence or absence of bacteria was evaluated macroscopically. Results: After 24 hours of incubation, 21.4% (n = 3) of the samples presented with a turbid appearance and after 48h, 71% (n = 10) of the samples presented with a turbid appearance and positive bacterial growth. Conclusion: The results suggest that IDDDs for topical medications may be important sources of contamination or recontamination of the nasal mucosa of individuals who are being treated for upper respiratory tract conditions. A better understanding of the risks of re-using IDDDs after previous contact with the nasal mucosa will improve guidelines on hygiene procedures and prevention of related risks.

Introdução: O uso de dispositivos intranasais para administração de medicamentos (IDDD) no tratamento da rinite alérgica (AR) é frequente, por serem simples, eficientes e seguros, e principalmente por serem de baixo risco. No entanto, especula-se que o contato entre a mucosa nasal e um IDDD possa causar infecções, uma vez que o nariz é colonizado por bactérias, e atualmente não há instruções adequadas para a higienização do IDDD. O objetivo deste estudo foi avaliar a possibilidade de contaminação de um IDDD para medicação tópica após simulação de uso em indivíduos saudáveis. Métodos: O estudo in vitro foi composto por 14 indivíduos saudáveis, de ambos os sexos, com idades entre 18 e 24 anos. As amostras foram coletadas imediatamente após a abertura de cada IDDD, e após a simulação do uso pelos sujeitos. Posteriormente, as amostras foram depositadas em tubos e mantidas em incubadora a 37 °C. Após 48 horas, as amostras foram inoculadas em ágar Müller-Hinton. As análises qualitativas da aparência das amostras foram realizadas após 24 e 48 horas, e após 72 horas a presença ou ausência de bactérias foi avaliada macroscopicamente. Resultados: Após 24 horas de incubação, 21,4% (n = 3) das amostras apresentaram aparência turva e, após 48h, 71% (n = 10) das amostras apresentaram aparência turva e crescimento bacteriano positivo. Conclusão: Os resultados sugerem que IDDDs para medicações tópicas podem ser importantes fontes de contaminação ou recontaminação da mucosa nasal de indivíduos em tratamento para condições do trato respiratório superior. Uma melhor compreensão dos riscos da reutilização de IDDDs após contato prévio com a mucosa nasal, melhorará as diretrizes sobre procedimentos de higiene e prevenção de riscos relacionados.

Comparison of topical and infiltration anesthesia for orthodontic mini-implant placement

Objective: To compare the acceptability and effectiveness of topical and infiltration anesthesia for placement of mini-implants used as temporary anchorage devices. Methods: The sample comprised 40 patients, 17 males and 23 females, whose mean age was 26 years old and who were all undergoing orthodontic treatment and in need for anchorage reinforcement. Mini-implants were bilaterally placed in the maxilla of all individuals, with infiltration anesthesia on one side and topical anesthesia on the other. These 40 patients completed two questionnaires, one before and another after mini-implant placement and pain was measured through a visual analog scale (VAS). The data collected were analyzed using descriptive statistics and the measurements of pain were compared by means of the non-parametric test of Mann-Whitney. Results: It was found that 60% of patients felt more comfortable with the use of topical anesthesia for mini-implant placement; 72.5% of patients described the occurrence of pressure during placement of the anchorage device as the most unpleasant sensation of the entire process; 62.5% of patients felt more pain with the use of topical anesthesia. Conclusion: It was concluded that patients had less pain with the use of infiltration anesthesia, and also preferred this type of anesthetic. .

Objetivo: comparar a aceitabilidade e a efetividade do uso de anestésico tópico e anestésico infiltrativo para inserção de mini-implantes ortodônticos, utilizados como dispositivos de ancoragem temporária. Métodos: foram selecionados 40 pacientes, sendo 17 do sexo masculino e 23 do sexo feminino, com idade média de 26 anos, todos em tratamento ortodôntico e necessitando de reforço de ancoragem. Em todos os indivíduos foram instalados mini-implantes bilateralmente em maxila, sendo em um dos lados com anestesia infiltrativa e do lado oposto com anestesia tópica. Esses 40 pacientes responderam dois questionários, sendo um pré- e outro pós-operatório, e foram obtidos índices de dor por meio da escala visual análoga (VAS). Os dados coletados foram analisados por meio de estatística descritiva e os índices de dor foram comparados por meio do teste não-paramétrico de Mann-Whitney. Resultados: verificou-se que 60% dos pacientes se sentiram mais confortáveis com a utilização de anestesia tópica para a inserção dos mini-implantes; 72,5% dos pacientes apontaram a pressão durante a inserção do dispositivo de ancoragem como a sensação mais desagradável de todo o processo; 62,5% dos pacientes sentiram mais dor com o uso de anestesia tópica. Conclusão: concluiu-se que os pacientes apresentaram menor índice de dor com o uso de anestesia infiltrativa e que, também, preferiram esse tipo de anestésico. .

Mucosal Immunization with Recombinant Adenovirus Encoding Soluble Globular Head of Hemagglutinin Protects Mice Against Lethal Influenza Virus Infection

Influenza virus is one of the major sources of respiratory tract infection. Due to antigenic drift in surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although hemagglutinin (HA) is one of the highly variable surface glycoproteins of the influenza virus, it remains the most attractive target for vaccine development against seasonal influenza infection because antibodies generated against HA provide virus neutralization and subsequent protection against the virus infection. Combination of recombinant adenovirus (rAd) vector-based vaccine and mucosal administration is a promising regimen for safe and effective vaccination against influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as vaccine candidate. The rAd vaccine was engineered to express high level of the protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based vaccine candidates induced significant levels of sustained HA-specific mucosal IgA and IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based influenza vaccine candidate for both efficacy and rapid production.

Induction of Mucosal Tolerance Using House Dust Mite-Cholera Toxin B Conjugate in Mouse Model of Allergic Rhinitis: Prophylactic and Long-Term Therapeutic Effects / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cholera toxin B (CTB) is an effective immunomodulating agent. Mucosal tolerance is a well recognized method for inducing tolerance, but large amounts of antigen is needed. The dosage required can be dramatically reduced through coupling the antigen to the CTB. This study aimed to examine whether mucosal administration of house dust mite coupled to CTB (HDM-CTB conjugate) would modulate specific type 1 hypersensitivity in the murine model of allergic rhinitis and to evaluate the prophylactic and long-term therapeutic effects. MATERIALS AND METHOD: C57BL/6 mice were sensitized with Dermatophagoides farinae extract. After administration of HDM-CTB conjugate, several parameters of allergic response were evaluated. RESULTS: After mucosal adminstration of HDM-CTB conjugate, allergic symptoms, eosinophilic infiltration into nasal mucosa, specific IgE, and the splenic T cell proliferation after Dermatophagoides farinae allergen challenge were suppressed. CONCLUSION: These findings show that HDM-CTB conjugate has an anti-allergic effect in the murine model of allergic rhinitis and suggest that house dust mite allergy can be modulated with mucosal administration of allergen coupled to CTB.

Modulation of Eosinophilia and Cytokines of Bronchoalveolar Larvage Fluid(BALF) by CpG Oligodeoxynucleotides(ODN) in a Mouse Model of Established Airway Inflammation / 소아알레르기및호흡기학회지

PURPOSE: Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Oligodeoxynucleotides containing a CpG motif(CpG ODN), as potent inducers of Th1 immunity, are considered promising candidates for immune modulation in asthma. In this study we wanted to investigate the effect of CpG ODN on eosinophilia and cytokines of BALF in a mouse model established airway inflammation and the optimal route(systemic vs mucosal) of CpG ODN. We examined the difference of immunologic responses between CpG ODN and corticosteroids. METHODS: Female BALB/c mice, induced pulmonary allergic inflammation, were treated intranasally or intraperitoneally with CpG ODN and Dexamethasone. Allergen-specific antibody responses, cytokines(IL-4, IL-5, IL-12), and eosinophilic inflammation of the airways were investigated on BALF and splenocyte. RESULTS: CpG ODN effectively induced IL-12 and inhibited IL-4 and IL-5 as well as eosinophilic inflammation when CpG ODN was administered intranasally or intraperitoneally with allergen challenge. Therapy with corticosteroides, while effective inhibiting IL-5 generation, did not induced IL-12 in BALF. CONCLUSION: Systemic or mucosal administration of CpG ODN effectively stimulated the production of Th1 cytokines and suppressed eosinophilic airway inflammation in contrast of corticosteroids and control ODN. Thus, CpG ODN vaccination is a potentially useful approach for immunomodulation of established airway inflammation in a mouse model of asthma.

Comparison of Intranasal and Sublingual Midazolam as a Preanesthetic Medication in Pediatric Patients / 대한마취과학회지

BACKGROUND: The perfect preanesthetic medication and its ideal route of administration are still debated. Transmucosal administration of midazolam has been of interest because of the rapid, reliable onset of action, predictable effects and avoidance of injections. Because many medications are well absorbed from the mucosa, we conducted a randomized, prospective, blinded study to compare acceptance and efficacy of intranasal and sublingual administration of midazolam as a preanesthetic medication in children. METHODS: One hundred twenty eight patients aged 0.5-12year were stratified by age: 38 infants and toddlers, 0.5-3yr; 48 preschoolers, 3.1-7yr; and 42 school age, 7.1-12yr. They were randomized to received 0.2 mg/kg of midazolam in the nose or under the tongue. Hemoglobin oxygen saturation by pulse oximetry and sedation score were recorded before drug administration, at 2.5min intervals for 15min, at separation from parents and during induction with enflurane in O2. Retention time of sublingual drug and duration of crying were recorded. RESULTS: The incidence of crying at the time of administration of midazolam was greater following intranasal compared with sublingual administration(60% vs 17%, p<0.05). Within age groups, only infants and toddlers showed a significant difference in the incidence of crying between treatment groups. Significant changes in sedation occured in both groups from 2.5min after administration. CONCLUSIONS: Sublingual midazolam is better accepted than intranasal midazolam as a preanesthetic sedative in children.