由于大分子量等因素,通过口服途径配制和递送大分子带来了相当大的挑战。pH敏感性,和有限的制定方法。如果药物渗透性差,这一挑战就会更加复杂,需要创新的药物输送策略。万古霉素,一种广泛使用的糖肽抗生素,口服生物利用度低于10%,主要导致静脉给药和潜在的患者不适。这项研究探讨了口腔途径作为一种非侵入性,高度血管化的替代给药途径,提供快速起效,同时绕过首过代谢。在这项研究中,使用等温干燥颗粒包衣机用L-谷氨酸包被万古霉素以调节通过口腔细胞系的渗透,TR146.结果证实了氨基酸浓度和干颗粒包衣对药物渗透性的速率和程度的显著影响。随着L-谷氨酸的引入和等温干式粒子涂布机的利用,由于药物离子对复合物的形成,万古霉素的渗透曲线比对照增加了六倍。成像研究显示在干包衣万古霉素颗粒的表面上存在分层的微粉化谷氨酸颗粒,这证实了干包衣和氨基酸浓度在调节药物渗透中的作用。金黄色葡萄球菌的微生物学实验,最小抑制浓度和生物膜破坏研究,提供了干包衣谷氨酸-万古霉素离子对颗粒结构的抗菌活性的确证证据。这项研究表明,第一次,口腔递送干包衣大分子药物,万古霉素,通过使用创新的颗粒涂层策略控制氨基酸的沉积。
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.