β-Lactoglobulin stabilized lipid nanoparticles enhance oral absorption of insulin by slowing down lipolysis  

作　　者：Lu Li Suticha Chunta Xianzi Zheng Haisheng He Wei Wu Yi Lu 

机构地区：[1]School of Pharmacy&Key Laboratory of Smart Drug Delivery of MOE,Fudan University,Shanghai 201203,China [2]Department of Clinical Chemistry,Faculty of Medical Technology,Prince of Songkla University,Songkhla 90110,Thailand [3]Shanghai Skin Disease Hospital,Tongji University School of Medicine,Shanghai 200433,China [4]Fudan Zhangjiang Institute,Shanghai 201203,China

出　　处：《Chinese Chemical Letters》2024年第4期287-291,共5页中国化学快报（英文版）

基　　金：funded by the Science and Technology Committee of Shanghai Municipality (Nos.19430741400, 23S11901500,23ZR1413100, and 21430760800);the National Natural Science Foundation of China (Nos.81973247 and 82030107)。

摘　　要：Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, including nanoemulsions(NE@β-lg) and nanocapsules(NC@β-lg), were developed to enhance the oral absorption of insulin by slowing down lipolysis due to the protection from β-lg. Cremophor EL stabilized nanoemulsions(NE@Cre-EL) were prepared and set as a control. The lipid nanoparticles produced mild and sustained hypoglycemic effects, amounting to oral bioavailability of 3.0% ± 0.3%, 7.0% ± 1.1%, and7.7% ± 0.8% for NE@Cre-EL, NE@β-lg, and NC@β-lg, respectively. Aggregation-caused quenching(ACQ)probes enabled the identification of intact nanoparticles, which were used to investigate the in vivo and intracellular fates of the lipid nanoparticles. In vitro digestion/lipolysis and ex vivo imaging confirmed delayed lipolysis from β-lg stabilized lipid nanoparticles. NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca^(2+)-induced crosslinking. Live imaging revealed the transepithelial transport of intact nanoparticles and their accumulation in the liver. Cellular studies confirmed the uptake of intact nanoparticles. Slowing down lipolysis via food proteins represents a good strategy to enhance the oral absorption of lipid nanoparticles and thus co-formulated biomacromolecules.

关 键 词：Β-LACTOGLOBULIN Lipid nanoparticles Oral absorption INSULIN LIPOLYSIS Aggregation-caused quenching 

分 类 号：R943[医药卫生—药剂学] TB383.1[医药卫生—药学]