Characterization of hyperbranched core-multishell nanocarriers as an innovative drug delivery system for the application at the oral mucosa
Characterization of hyperbranched core-multishell nanocarriers as an innovative drug delivery system for the application at the oral mucosa
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DOI：
10.1111/jre.12487
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发表时间：
2018-02-01
影响因子：
3.5
通讯作者：
Dommisch, H.
中科院分区：
文献类型：
--
作者：
Jager, J.;Obst, K.;Dommisch, H.
背景和目的在口腔中，粘膜组织可能会出现许多不同的病理状况，例如需要治疗的炎症性疾病（牙龈炎、牙周炎）和自身免疫性疾病（例如口腔扁平苔藓）。局部药物的应用是一种常见的治疗方法。然而，它们的功效是有限的。唾液的稀释作用阻碍了药物制剂的粘附和渗透。因此，口服局部药物的生物利用度不足，患者即使不是终身，也可能会多年患病。 材料和方法在本研究中，我们表征了核-多壳（CMS）纳米载体作为口腔粘膜组织药物递送系统的潜在用途。为此，我们准备了猪咀嚼粘膜和颊粘膜并进行了弗朗兹细胞扩散实验。使用共焦激光扫描显微镜分析荧光标记的 CMS 纳米载体对粘膜组织的渗透。暴露于 CMS 纳米载体后，分别通过 MTT 和磺基罗丹明 B 测定测定牙龈上皮细胞的代谢和增殖活性。结果在这里，我们可以表明载体渗透到两种粘膜组织中，而颗粒则渗透到咀嚼粘膜更深处。电子顺磁共振波谱显示，装载到CMS纳米载体上的3-羧基-2,2,5,5-四甲基-1-吡咯烷氧基标记的糖皮质激素地塞米松在两种粘膜组织中均从载体中释放，但在颊粘膜中的效率更高。在这两种情况下，纳米载体的释放均优于传统乳膏的释放，传统乳膏通常用于治疗口腔炎症。 CMS纳米载体在体外既没有表现出细胞毒性也没有增殖作用。结论这些研究结果表明CMS纳米载体可能是治疗口腔炎症性疾病的局部药物递送的创新方法。
Background and ObjectivesIn the oral cavity, the mucosal tissues may develop a number of different pathological conditions, such as inflammatory diseases (gingivitis, periodontitis) and autoimmune disorders (eg, oral lichen planus) that require therapy. The application of topical drugs is one common therapeutic approach. However, their efficacy is limited. Dilution effects due to saliva hinder the adherence and the penetration of drug formulations. Therefore, the bioavailability of oral topical drugs is insufficient, and patients may suffer from disease over years, if not life-long.Material and MethodsIn the present study, we characterized core-multishell (CMS) nanocarriers for their potential use as drug delivery systems at oral mucosal tissues. For this purpose, we prepared porcine masticatory as well as buccal mucosa and performed Franz cell diffusion experiments. Penetration of fluorescently labeled CMS nanocarriers into the mucosal tissue was analyzed using confocal laser scanning microscopy. Upon exposure to CMS nanocarriers, the metabolic and proliferative activity of gingival epithelial cells was determined by MTT and sulforhodamine B assays, respectively.ResultsHere, we could show that the carriers penetrate into both mucosal tissues, while particles penetrate deeper into the masticatory mucosa. Electron paramagnetic resonance spectroscopy revealed that the 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy-labeled glucocorticoid dexamethasone loaded on to the CMS nanocarriers was released from the carriers in both mucosal tissues but with a higher efficiency in the buccal mucosa. The release from the nanocarriers is in both cases superior compared to the release from a conventional cream, which is normally used for the treatment of inflammatory conditions in the oral cavity. The CMS nanocarriers exhibited neither cytotoxic nor proliferative effects in vitro.ConclusionThese findings suggested that CMS nanocarriers might be an innovative approach for topical drug delivery in the treatment of oral inflammatory diseases.