RESUMEN
The formulation and delivery of macromolecules through the oral route pose considerable challenges due to factors such as large molecular weight, pH sensitivity, and limited formulation approaches. This challenge is compounded if the drug is poorly permeable, necessitating innovative drug delivery strategies. Vancomycin, a widely prescribed glycopeptide antibiotic, has an oral bioavailability of less than 10%, leading to predominantly intravenous administration and potential patient discomfort. This study explores the potential of the buccal route as a non-invasive, highly vascularised alternative route of administration, offering a rapid onset of action while bypassing the first-pass metabolism. In this study, vancomycin was coated with L-glutamic acid using an isothermal dry particle coater to modulate permeation through the buccal cell line, TR146. Results confirm significant impact of both amino acid concentration and dry particle coating on the rate and extent of drug permeability. With the introduction of L-glutamic acid and utilisation of the isothermal dry particle coater, vancomycin's permeation profile increased six-fold compared to the control due to the formation of drug ion-pair complex. Imaging studies showed the presence of layered micronized glutamic acid particles on the surface of dry coated vancomycin particles which confirms the role of dry coating and amino acid concentration in modulating drug permeation. Microbiology experiments in Staphylococcus aureus, minimum inhibitory concentration and biofilm disruption studies, provided confirmatory evidence of antimicrobial activity of dry coated glutamic acid-vancomycin ion pair particulate structure. This study demonstrates, for the first-time, buccal delivery of dry coated large molecule drug, vancomycin, through controlled deposition of amino acid using innovative particle coating strategy.
Asunto(s)
Antibacterianos , Vancomicina , Vancomicina/administración & dosificación , Vancomicina/farmacocinética , Humanos , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/farmacocinética , Aminoácidos/química , Aminoácidos/metabolismo , Staphylococcus aureus/efectos de los fármacos , Mucosa Bucal/metabolismo , Permeabilidad/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Línea Celular , Ácido Glutámico/metabolismoRESUMEN
The diagnosis of enteric neuromuscular disorders has come a long way since the first description of an enteric neuropathic disorder by the Danish physician Harald Hirschsprung in 1886. Advances in specialized enteric histopathological staining techniques have made it possible to identify subtle neuropathies and myopathies that cause intestinal motility disorders, from the common and now better understood and relatively easily diagnosed Hirschsprung's disease to the less common and more severe and not well-characterized chronic idiopathic intestinal pseudoobstruction, which continues to present a diagnostic challenge to the gastroenterologist and histopathologist alike. This article will discuss the common gastrointestinal motility disorders and some of the specialized histological stains, such as the relatively common enzyme stain, acetylcholinesterase, used to diagnose Hirschsprung's disease; advanced tinctorial stains, such as Masson trichrome, which may aid in diagnosis of enteric myopathies causing pseudoobstruction; and immunohistochemical stains such as C-Kit or PG 9.5, which may aid in the diagnosis of enteric neuropathies causing pseudoobstruction.
Asunto(s)
Enfermedades Gastrointestinales/diagnóstico , Motilidad Gastrointestinal/fisiología , Sistema Nervioso Entérico/patología , Acalasia del Esófago/diagnóstico , Enfermedades Gastrointestinales/fisiopatología , Tracto Gastrointestinal/inervación , Gastroparesia/diagnóstico , Enfermedad de Hirschsprung/diagnóstico , Humanos , Seudoobstrucción Intestinal/diagnóstico , Coloración y Etiquetado/métodosRESUMEN
Sarcomatoid carcinoma of the small bowel is rare; to our knowledge, 19 cases have been reported to date in the English literature under several names. We report an additional case occurring in the jejunum of a 55-year-old man. The tumor was a polypoid 7.5-cm mass, which infiltrated the full thickness of the intestinal wall and the serosa of an adhesed loop of small bowel. On microscopic examination, the neoplasm was composed of sheets of spindle cells; focally, an anaplastic component was present, including tumor giant cells with bizarre nuclei. On immunohistochemical stains, tumor cells were positive for cytokeratin 7, cytokeratin AE1/AE3, vimentin, and focally, epithelial membrane antigen. No staining for cytokeratin 20 was found. Sarcomatoid carcinoma must be kept in mind in the differential diagnosis of malignant spindle cell tumors of the small bowel. As consensus regarding the terminology of these rare tumors is being reached, immunohistochemical stains are essential for accurate diagnosis.