Insulin nanoparticles (NPs) were prepared by pH-shift precipitation and a newly developed disassembly method at room temperature. Then, an electrostatic interaction-based, layer-by-layer (LbL) multilayer film incorporating insulin NPs was fabricated with poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH), which is described herein as Si/(PAH/PAA)5(PAH/PAA-insulin NPs)n. The positively charged insulin NPs were introduced into the LbL film in the form of biocompatible PAA-insulin NP aggregates at a pH of 4.5 and were released in phosphate-buffered saline (pH 7.4), triggered by changes in the charges of the insulin molecules. In addition, the insulin-incorporated multilayer was swollen because of the different ionic environment, leading also to insulin release. Eighty percent of the insulin was released from the LBL film in the first stage of 3 h, and sustained release could be maintained in the second stage for up to 7 days in vitro, which is very critical for specific diabetic patients. These striking findings could offer novel directions to researchers in establishing insulin delivery systems for diabetic therapy and fabricating other protein nanoparticles applied to various biomedical platforms.
Bibliographical noteFunding Information:
This research was supported by the National Research Foundation of Korea (NRF) , funded by the Ministry of Science, ICT & Future Planning ( NRF-2013R1A1A1076126 , and 2012M3A9C6050104 ). Additionally, this work was also supported by a grant from the Next-Generation BioGreen 21 Program (No. PJ009986012015 ) ( Rural Development Administration , Republic of Korea), as well as the High Value-added Food Technology Development Program of the Ministry of Agriculture, Food and Rural Affairs ( 114027-03-1-HD020 ) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry of Health & Welfare ( HI14C-3266-030014 ).
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Condensed Matter Physics
- Mechanics of Materials
- Mechanical Engineering