A sustained zero-order release carrier for long-acting, peakless basal insulin therapy.
Yuanpeng WangMian FuZuwei WangJulian X X ZhuYing GuanYongjun ZhangPublished in: Journal of materials chemistry. B (2021)
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 ∼16 days. Initial burst release, a severe problem for other release systems, was successfully avoided.
Keyphrases
- type diabetes
- glycemic control
- blood glucose
- room temperature
- insulin resistance
- drug delivery
- reduced graphene oxide
- emergency department
- drug induced
- oxidative stress
- gold nanoparticles
- stem cells
- diabetic rats
- metabolic syndrome
- replacement therapy
- diabetic nephropathy
- high frequency
- early onset
- single cell
- optical coherence tomography
- data analysis
- wound healing
- cell therapy