Li Shuzhen, Li Wanqiong, Yang Xin, Gao Yanfeng, Chen Guanyu
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.
Pharmaceutics. 2022 Dec 19;14(12):2844. doi: 10.3390/pharmaceutics14122844.
Oral delivery is the most convenient drug administration route. However, oral delivery of peptides is extremely challenging due to the physical and chemical barriers within the gastrointestinal tract. Polysaccharides are often utilized as polymeric biomaterials in drug delivery. Among these, dietary polysaccharides extracted from okra, yam, and spirulina have been reported to stimulate innate immunity with well-known nutritional benefits. In this study, we developed a dietary-polysaccharide-modified fish-oil-based emulsion for oral co-delivery of a hydrophilic PD-L1 blocking peptide and the hydrophobic small molecule simvastatin. The optimal emulsion was nano-sized and exhibited a negative surface charge, high drug encapsulation efficiency of over 97%, low viscosity, and sustained drug release manner. The formulation could significantly increase the uptake of peptides by intestinal Caco-2 cells, which demonstrated the great potential of the formulation for promoting the oral absorption of peptides. Additionally, these dietary polysaccharides could promote dendritic cell maturation and cytokine expression in macrophages, demonstrating that these nutraceutical polysaccharides had dual roles of functioning as promising colloidal delivery systems and as potential immune modulators or adjuvants. Thus, this food-based colloidal delivery system shows promise for the oral delivery of peptide drugs and lays a great platform for future applications in immunotherapy.
口服给药是最方便的药物给药途径。然而，由于胃肠道内的物理和化学屏障，肽类药物的口服给药极具挑战性。多糖常被用作药物递送中的聚合物生物材料。其中，从秋葵、山药和螺旋藻中提取的膳食多糖已被报道具有刺激先天免疫的作用，并具有众所周知的营养益处。在本研究中，我们开发了一种基于膳食多糖修饰的鱼油乳液，用于口服共递送亲水性PD-L1阻断肽和疏水性小分子辛伐他汀。最佳乳液为纳米尺寸，表面带负电荷，药物包封率超过97%，粘度低，药物释放方式持续。该制剂可显著提高肠道Caco-2细胞对肽的摄取，这表明该制剂在促进肽类药物口服吸收方面具有巨大潜力。此外，这些膳食多糖可促进树突状细胞成熟和巨噬细胞中细胞因子的表达，表明这些营养保健品多糖具有作为有前景的胶体递送系统以及潜在免疫调节剂或佐剂的双重作用。因此，这种基于食物的胶体递送系统在肽类药物口服递送方面显示出前景，并为免疫治疗的未来应用奠定了良好的平台。
