Dual-controlled oral colon-targeted delivery of bovine insulin based on mesoporous phosphonate

• We developed a time- and pH-controlled oral colon-targeted delivery system for insulin.
• Dip-coating lag-time films on tablet comprising an insulin-loaded pH-sensitive mesoporous phosphonate core and outer absorption enhancer.
• The new delivery system can protect insulin passing through stomach and small intestine, as well as deliver insulin targeting the colon.
• The combination of pH-sensitive mesoporous phosphonate with coating technology could be extended in oral delivery of other therapeutic proteins.

The time- and pH-controlled oral colon-targeted delivery system for bovine insulin was developed by dip-coating lag-time films on tablet comprising bovine insulin-loaded pH-sensitive mesoporous phosphonate (ZrBPMP-3) as tablet core and absorption enhancer of insulin, sodium glycocholate, in outer layer, in which the lag time can be controlled via adjusting coating times of lag-time films and the release of bovine insulin in the colon can be triggered by pH-sensitive ZrBPMP-3. The pH transition release experiments show that the tablet with four times lag-time films coating can carry bovine insulin passing through the stomach and small intestine with a minimum release and trigger off the release of loaded bovine insulin in the colon under dual control, time control and pH value control. Furthermore, the released bovine insulin can still retain its native conformation, as evidenced by circular dichroism spectroscopy, indicating that bovine insulin cannot denature and lose its bioactive conformation during the loading, lag-time films coating, delivery and release. In addition, it is worth mentioning that ZrBPMP-3 almost exhibits non-cytotoxicity at low concentration in MTT assays. Thus, ZrBPMP-3 as a new kind of carrier and based on which developing controllable colon-targeted delivery system have potential application in oral delivery of insulin and even other therapeutic peptides and proteins.

The time- and pH-controlled oral colon-targeted delivery system for bovine insulin has been designed and developed by dip-coating lag-time films on tablet comprising bovine insulin-loaded pH-sensitive mesoporous phosphonate as tablet core and absorption enhancer of insulin, sodium glycocholate, in outer layer. The new drug delivery system can protect bovine insulin passing through the stomach and small intestine, as well as deliver bovine insulin and its absorption enhancer targeting the colon, which helps to improve delivery efficiency, bioactivity conservation and bioavailability of bovine insulin through time and pH value dual-controlled release, lag-time films coating and carrying absorption enhancer along with bovine insulin at the same time, respectively. Furthermore, the combination of pH-sensitive mesoporous phosphonate with lag-time films coating technology could be readily applied in oral delivery of other therapeutic peptides and proteins.Figure optionsDownload as PowerPoint slide