Department of Pharmaceutics, College of Pharmacy, University of Sulaimani, Sulaimani, 46001 Kurdistan Region, Iraq; Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK.
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland; Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK.
J Colloid Interface Sci. 2022 Nov 15;626:251-264. doi: 10.1016/j.jcis.2022.06.126. Epub 2022 Jun 27.
Transmucosal administration offers numerous advantages for drug delivery as it usually helps to avoid first pass metabolism, provides rapid onset of action, and is a non-invasive route. Mucosal surfaces are covered by a viscoelastic mucus gel layer which acts as a protective barrier preventing the entrance of harmful substances into the human tissues. This function of mucus also inhibits the diffusion of drugs and nano-formulations and can result in a significant reduction of their efficacy. The design of mucus-penetrating nanoparticles can overcome the barrier function of mucus which may lead to better therapeutic outcomes. In this study, chitosan was chemically modified by grafting short chains of poly(ethylene glycol), poly(2-hydroxyethyl acrylate), poly(2-ethyl-2-oxazoline), or poly(N-vinyl pyrrolidone) and the resulting chitosan derivatives were used to prepare nanoparticles using an ionic gelation method with sodium tripolyphosphate. These nanoparticles were characterised using dynamic light scattering, transmission electron microscopy, small-angle neutron scattering and nanoparticle tracking analysis. Small-angle neutron scattering data revealed the presence of a large amount of water inside these nanoparticles and lack of a heterogeneous internal structure. The nanogel model with low crosslinking density is suggested as the most feasible model to describe the structure of these nanoparticles. The studies of the behaviour of these nanoparticles in bovine submaxillary mucin solutions and their penetration into sheep nasal mucosa indicated greater diffusivity of modified chitosan nanoparticles compared to unmodified chitosan nanoparticles with the best results achieved for the chitosan grafted with poly(N-vinyl pyrrolidone).
黏膜给药为药物输送提供了众多优势，因为它通常有助于避免首过代谢，提供快速的作用开始，并且是非侵入性途径。黏膜表面被一层粘弹性黏液凝胶层覆盖，该层作为保护性屏障，防止有害物质进入人体组织。黏液的这种功能还抑制了药物和纳米制剂的扩散，可导致其功效显著降低。设计能够克服黏液屏障功能的黏膜穿透纳米颗粒可能会带来更好的治疗效果。在这项研究中，壳聚糖通过接枝短链聚乙二醇、聚（2-羟乙基丙烯酸酯）、聚（2-乙基-2-恶唑啉）或聚（N-乙烯基吡咯烷酮）进行了化学修饰，并用三聚磷酸钠通过离子凝胶化方法制备了这些壳聚糖衍生物的纳米颗粒。使用动态光散射、透射电子显微镜、小角中子散射和纳米颗粒跟踪分析对这些纳米颗粒进行了表征。小角中子散射数据显示这些纳米颗粒内部存在大量的水，并且缺乏不均匀的内部结构。低交联密度的纳米凝胶模型被认为是描述这些纳米颗粒结构的最可行模型。在牛颌下黏液溶液中和穿透绵羊鼻黏膜中这些纳米颗粒的行为研究表明，与未修饰的壳聚糖纳米颗粒相比，修饰的壳聚糖纳米颗粒具有更大的扩散性，其中接枝聚（N-乙烯基吡咯烷酮）的壳聚糖的效果最好。
