Abstract
Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and pep-tides,but delivery efficiency is compromised by lipolysis.β-Lactoglobulin(β-lg)stabilized lipid nanopar-ticles,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 sta-bilized 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％,and 7.7％±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 de-layed lipolysis from β-lg stabilized lipid nanoparticles.NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca2+-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.
基金项目
Science and Technology Com-mittee of Shanghai Municipality(19430741400)
Science and Technology Com-mittee of Shanghai Municipality(23S11901500)
Science and Technology Com-mittee of Shanghai Municipality(23ZR1413100)
Science and Technology Com-mittee of Shanghai Municipality(21430760800)
国家自然科学基金(81973247)
国家自然科学基金(82030107)
NETL
NSTL
万方数据