Université Paris Est, ICMPE (UMR 7182), CNRS, UPEC, F-94320 Thiais, France.
INSERM U955, Equipe 21, Centre de Référence Syndrome Néphrotique Idiopathique UPEC Créteil France.
Colloids Surf B Biointerfaces. 2019 Jul 1;179:128-135. doi: 10.1016/j.colsurfb.2019.03.060. Epub 2019 Mar 28.
Most of the drug molecules are partially insoluble in aqueous solution and then may accumulate in fat tissues hampering efficient therapy. Innovative drug delivery strategies have emerged in industry or academia over the last decades, however preserving the activity of the encapsulated drug, having high drug loading capacity and controlling drug release kinetics, are still challenging. In this context, we explored the preparation of new nanocarriers, namely nanocapsules, via a templating method, and using polysaccharides exhibiting biological functions. Cationic poly(cyclodextrin) (P(CD)) and alginate (alg) were initially self-assembled layer-by-layer on colloidal gold nanoparticles. Removal of gold nanoparticles was then induced thorough cyanide-assisted hydrolysis, enabling the recovery of nanocapsules. A hydrophobic drug known to allow the mutation of genes inside cells, namely 4-hydroxy-tamoxifen, was loaded within the nanocapsules' shell via inclusion with the cyclodextrin cavities. The so-designed nanomaterials were incubated with immortalized podocytes to investigate i) their incorporation inside cells and ii) their efficiency for in vitro 4-hydroxy-tamoxifen-induced CreERT2 recombination. This work undoubtedly highlights a proof-of-concept for drug delivery using polysaccharides-based capsules with host properties.
大多数药物分子在水溶液中部分不溶,然后可能在脂肪组织中积累,从而阻碍有效的治疗。在过去几十年中,行业和学术界已经出现了创新的药物输送策略,然而,保持包裹药物的活性、具有高载药能力和控制药物释放动力学仍然具有挑战性。在这种情况下,我们探索了通过模板法制备新的纳米载体,即纳米胶囊,并使用具有生物功能的多糖。阳离子聚(环糊精)(P(CD))和藻酸盐(alg)最初通过层层自组装在胶体金纳米粒子上。然后通过氰化物辅助水解诱导金纳米粒子的去除,从而实现纳米胶囊的回收。一种已知能够使细胞内基因发生突变的疏水性药物,即 4-羟基他莫昔芬,通过与环糊精腔的包合作用被负载在纳米胶囊壳内。所设计的纳米材料与永生化足细胞孵育,以研究 i)它们在细胞内的掺入情况和 ii)它们在体外 4-羟基他莫昔芬诱导 CreERT2 重组中的效率。这项工作无疑突出了使用具有主体性质的基于多糖的胶囊进行药物输送的概念验证。