Giannola Libero Italo, De Caro Viviana, Giandalia Giulia, Siragusa Maria Gabriella, Campisi Giuseppina, Florena Ada Maria, Ciach Tomasz
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Eur J Pharm Biopharm. 2007 Feb;65(2):238-46. doi: 10.1016/j.ejpb.2006.07.004. Epub 2006 Jul 26.
In transbuccal absorption a major limitation could be the low permeability of the mucosa which implies low drug bioavailability. The ability of naltrexone hydrochloride (NLX) to penetrate a resembling histologically human buccal mucosa was assessed and the occurrence of any histomorphological changes observed. We used reconstituted human oral (RHO) non-keratinised epithelium as mucosal section and a Transwell diffusion cells system as bicompartmental model. Buccal permeation was expressed in terms of drug flux (J(s)) and permeability coefficients (K(p)). Data were collected using both artificial and natural human saliva. The main finding was that RHO does not restrain NLX permeation. Drug transport across the epithelium was observed also in presence of various concentrations of penetration enhancers, without any significant differences. On the contrary, the flux throughout the mucosa was extensively affected by iontophoresis. Histologically, no sign of flogosis was observed in any specimen under experiment without iontophoresis, whereas cytoarchitectural changes, up to nuclear pycnosis or cellular swelling, were determined as a consequence of the application of electric fields.
在经颊吸收中，一个主要限制可能是黏膜的低渗透性，这意味着药物生物利用度较低。评估了盐酸纳曲酮（NLX）穿透组织学上类似人类颊黏膜的能力，并观察了任何组织形态学变化的发生情况。我们使用重组人口腔（RHO）非角化上皮作为黏膜切片，并使用Transwell扩散池系统作为双室模型。颊部渗透以药物通量（J(s)）和渗透系数（K(p)）表示。使用人工唾液和天然人类唾液收集数据。主要发现是RHO不会抑制NLX的渗透。在存在各种浓度的渗透促进剂的情况下，也观察到药物跨上皮运输，没有任何显著差异。相反，整个黏膜的通量受到离子电渗疗法的广泛影响。在组织学上，在没有离子电渗疗法的任何实验标本中均未观察到炎症迹象，而由于施加电场，确定了细胞结构变化，直至核固缩或细胞肿胀。
