d'Angelo Ivana, Fraix Aurore, Ungaro Francesca, Quaglia Fabiana, Miro Agnese
Department of Environmental, Biological and Pharmaceutical Science and Technology, University of Campania "Luigi Vanvitelli", Via A. Vivaldi, 43, 81100 Caserta, Italy.
Department of Drug Sciences, University of Catania, Viale A. Doria, 6, 95125, Catania, Italy.
Int J Pharm. 2017 Oct 15;531(2):606-613. doi: 10.1016/j.ijpharm.2017.06.029. Epub 2017 Jun 12.
In this study, we highlight the potential of the mucoadhesive film made from a poly(ethylene oxide)/hydroxypropyl-β-cyclodextrin (PEO/CD) mixture in the oromucosal delivery of hydrophilic drugs, with a specific focus on dexamethasone phosphate disodium salt (Dexa). CD formed a complex with Dexa in solution and did not interact with mucin as highlighted from the spectrophotometric and spectrofluorimetric analysis. Similarly, CD and PEO did not affect mucin conformation, suggesting no direct interaction between the unstirred water layer and film components. Remarkably, PEO/CD/Dexa films dissolved more slowly than those made of PEO alone also in phosphate-buffered saline (PBS) pH 6.8 and gave a time-control on Dexa delivered dose. These combined effects resulted in a higher amount of Dexa accumulated in the mucosa, which can be highly beneficial in case of local diseases. Furthermore, Dexa amount able to diffuse through porcine buccal mucosa was lower when film contained CD, highlighting how CD can act as a modulator of drug transport also in the case of water-soluble drugs. In summary, our results demonstrate the versatility of PEO/CD films in mucosal delivery of hydrophilic corticosteroids paving the way to a novel approach in the treatment of mouth diseases.
在本研究中，我们强调了由聚环氧乙烷/羟丙基-β-环糊精（PEO/CD）混合物制成的粘膜粘附膜在亲水性药物口腔粘膜给药方面的潜力，特别关注地塞米松磷酸二钠盐（地塞米松）。通过分光光度法和荧光分光光度法分析表明，CD在溶液中与地塞米松形成复合物，且不与粘蛋白相互作用。同样，CD和PEO不影响粘蛋白构象，这表明在未搅拌水层与膜成分之间不存在直接相互作用。值得注意的是，在pH 6.8的磷酸盐缓冲盐水（PBS）中，PEO/CD/地塞米松膜的溶解速度也比单独由PEO制成的膜更慢，并且对地塞米松的给药剂量具有时间控制作用。这些综合效应导致更多的地塞米松积聚在粘膜中，这对于局部疾病可能非常有益。此外，当膜中含有CD时，能够扩散通过猪颊粘膜的地塞米松量较低，这突出了CD在水溶性药物情况下也可作为药物转运调节剂的作用。总之，我们的结果证明了PEO/CD膜在亲水性皮质类固醇粘膜给药方面的多功能性，为口腔疾病治疗开辟了一种新方法。
