期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 8, 期 9, 页码 1952-1959出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9tb02728a
关键词
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资金
- National Natural Science Foundation of China [51625302, 51873091]
- National Key Research and Development Program of China [2017YFC1103501]
Basal insulin therapy plays a key role in diabetes management. An ideal therapy should mimic the steady physiologic basal insulin secretion, and provide a peak-free, prolonged and steady insulin supply. Herein, a new drug carrier was designed by first PEGylating insulin and then incorporating the conjugate into layer-by-layer assembled films with tannic acid (TA). Because PEG-insulin and TA in the films were linked with reversible, dynamic hydrogen bonds, the films disintegrate gradually when soaked in aqueous solutions, and thus release PEG-insulin into the media. In vitro release tests revealed that the release of PEG-insulin follows a zero-order kinetics. Theoretical analysis based on the unique release mechanism also supports a zero-order kinetics. In vivo tests using a streptozotocin-induced diabetic rat model demonstrated that subcutaneous implantation of the film could maintain a steady plasma drug level and hence maintain a fasting blood glucose level (BGL) close to normal. The duration of action depends on the thickness of the film. Using a 50-bilayer film, fasting BGL was kept within the normoglycemic range for similar to 16 days. Initial burst release, a severe problem for other release systems, was successfully avoided.
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