Lin Chi, Hsu Fang-Yu, Lin Wei-Ting, Cha Chia-Yun, Ho Yi-Cheng, Mi Fwu-Long
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Polymers (Basel). 2022 Jul 21;14(14):2966. doi: 10.3390/polym14142966.
polysaccharides (OJPs) have great anti-inflammation and immunomodulatory abilities. However, the low bioavailability of OJPs reduces its applicability in the biomedical and pharmaceutical fields. Chitosan (CS) has excellent mucoadhesive properties and absorption-enhancing ability in oral administration. Casein hydrolysate (CL) has good interfacial diffusivity and emulsifying ability, and can interact with polysaccharides to form complexes combining the individual properties of both. Therefore, chitosan and casein hydrolysate are good candidates for developing nanoformulations for oral delivery. In this study, bioactive polysaccharides (OJPs), CS and CL, were combined to prepare CS/OJPs/CL co-assembled biodegradable nanoparticles. The interactions between polysaccharides (CS and OJPs) and peptide (CL) resulted in the formation of nanoparticles with an average particle size of 198 nm and high OJPs loading efficiency. The colloidal properties of the nanoparticles were pH-dependent, which were changed significantly in simulated digestive fluid at different pH values. OJPs released from the CS/OJPs/CL nanoparticles were greatly affected by pH and enzymatic degradation (trypsin and lysozyme). The nanoparticles were easily internalized by macrophages, thereby enhancing the OJPs' inhibitory ability against Ni-induced cytotoxicity and LPS-induced nitric oxide production. This study demonstrates that prepared polysaccharide/protein co-assembled nanoparticles can be potential nanocarriers for the oral delivery of bioactive polysaccharides with anti-inflammatory functions.
多糖（OJPs）具有很强的抗炎和免疫调节能力。然而，OJPs的低生物利用度降低了其在生物医学和制药领域的适用性。壳聚糖（CS）在口服给药方面具有优异的粘膜粘附性能和吸收增强能力。酪蛋白水解物（CL）具有良好的界面扩散性和乳化能力，并且可以与多糖相互作用形成结合两者各自特性的复合物。因此，壳聚糖和酪蛋白水解物是开发口服递送纳米制剂的良好候选材料。在本研究中，将生物活性多糖（OJPs）、CS和CL组合制备CS/OJPs/CL共组装可生物降解纳米颗粒。多糖（CS和OJPs）与肽（CL）之间的相互作用导致形成平均粒径为198nm且OJPs负载效率高的纳米颗粒。纳米颗粒的胶体性质依赖于pH值，在不同pH值的模拟消化液中会发生显著变化。从CS/OJPs/CL纳米颗粒中释放的OJPs受到pH值和酶降解（胰蛋白酶和溶菌酶）的极大影响。纳米颗粒很容易被巨噬细胞内化，从而增强了OJPs对镍诱导的细胞毒性和脂多糖诱导的一氧化氮产生的抑制能力。本研究表明，制备的多糖/蛋白质共组装纳米颗粒可能是用于口服递送具有抗炎功能的生物活性多糖的潜在纳米载体。
