Abstract
Oral therapeutic agents offer the advantages of greater convenience, ease of administration, and their associated complications and costs. Among all of the oral therapeutic agents, nearly half of the drug candidates have poor water solubility, and oral delivery of such drugs is limited by difficulties, including poor solubility, low permeability, instability, and rapid metabolism, all of which cause low oral bioavailability. To address these issues, we developed a bubbles carrier system which including a foaming agent (FA) —sodium bicarbonate (SBC), diethylene triamine pentaacetic acid (DTPA) dianhydride, a surfactant (sodium dodecyl sulfate, SDS) together with hydrophobic drug (curcumin). The powder mixture can self-assembly undergo 3-stage structural transformations after encountering intestinal fluid: First, the test powder produces a CO2 bubble carrier system in aqueous phase where curcumin encapsulated in the hydrophobic tail of SDS. Next, these bubble carriers gradually float to the air-water interface due to their density with structural transition of which curcumin is distributed from single layer to double layer once exposing to air. Finally, those of bubble carriers burst owing to their surface tension, and followed by a curcumin loaded missiles with a particle size range around 300~1200 nm mechanically emulsified in aqueous water. This carrier system can facilitate curcumin uptake through M-cellular endocytosis, which locate on the intestinal tract and can be visualized by CLSM. Afterward, the TEM and IVIS results suggested that those of delivered curcumin were underwent lymphocyte and then were specifically shipped into lymphatic system nearby pancreas tissue through the lymphatic drainage between intestinal and pancreas lymphatic channel. It is a niche to orally treat pancreas disease like pancreatitis. To evaluate the in vivo efficacy of this curcumin loaded carrier system via oral administration, we induced a pancreatitis rat model and elucidated their antipancreatitis ability by measuring plasma IL-6 and amylase ELISA after ingesting the test enteric coated capsule. Histological analysis of the harvested pancreas also was used in pharmacodynamics study. Our results clearly evidenced that the developed carrier system may enhance curcumin absorption and enable to significantly suppression pancreatitis via oral administration. Therefore, this carrier system is expected to apply to other hydrophobic drugs and specifically delivers hydrophobic drugs into the lymphatic system orally in the future research.