Di Cola Emanuela, Cantu' Laura, Brocca Paola, Rondelli Valeria, Fadda Giulia C, Canelli Elena, Martelli Paolo, Clementino Adryana, Sonvico Fabio, Bettini Ruggero, Del Favero Elena
Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, via fratelli Cervi 93, 20900 Segrate (Mi), Italy; Institute Laue-Langevin (ILL), 71 avenue des Martyrs, CS 20156, 38042 Grenoble Cedex 9, France.
Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, via fratelli Cervi 93, 20900 Segrate (Mi), Italy.
Colloids Surf B Biointerfaces. 2019 Nov 1;183:110439. doi: 10.1016/j.colsurfb.2019.110439. Epub 2019 Aug 15.
We propose novel oil-in-water nanoemulsions (O/W NEs) including PEGylated surfactants and chitosan, showing good biocompatibility and optimization for nasal administration of drugs or vaccines. The transmucosal route has been shown to be ideal for a fast and efficient absorption and represents a viable alternative when the oral administration is problematic. The critical structural features in view of optimal encapsulation and transmucosal delivery were assessed by characterizing the NEs with complementary scattering techniques, i.e. dynamic light scattering (DLS), small angle X-ray (SAXS) and neutron scattering (SANS). Combined results allowed for selecting the formulations with the best suited structural properties and in addition establishing their propensity to enter the mucus barrier. To this scope, mucin was used as a model system and the effect of adding chitosan to the NEs, as adjuvant, was investigated. Remarkably, the presence of chitosan had a positive impact on the diffusion of the NE particles through the mucin matrix. We can infer that chitosan-mucin interaction induces density inhomogeneity and an increase in the pore size within the gel matrix that enhances the PEGylated NEs mobility. The coupling of mucoadhesive and mucopenetrating agents is shown to be a promising strategy for innovative transmucosal delivery systems.
我们提出了新型水包油纳米乳剂（O/W NEs），其包含聚乙二醇化表面活性剂和壳聚糖，具有良好的生物相容性，并且针对药物或疫苗的鼻腔给药进行了优化。经黏膜途径已被证明是实现快速有效吸收的理想途径，并且在口服给药存在问题时是一种可行的替代方案。通过使用互补散射技术，即动态光散射（DLS）、小角X射线散射（SAXS）和中子散射（SANS）对纳米乳剂进行表征，评估了实现最佳包封和经黏膜递送的关键结构特征。综合结果有助于选择具有最适合结构特性的制剂，此外还能确定它们进入黏液屏障的倾向。为此，使用黏蛋白作为模型系统，并研究了向纳米乳剂中添加壳聚糖作为佐剂的效果。值得注意的是，壳聚糖的存在对纳米乳剂颗粒通过黏蛋白基质的扩散有积极影响。我们可以推断，壳聚糖 - 黏蛋白相互作用会导致密度不均匀，并使凝胶基质内的孔径增加，从而增强聚乙二醇化纳米乳剂的流动性。黏附剂和黏液穿透剂的结合被证明是创新经黏膜递送系统的一种有前景的策略。
