Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs
Authors: Robert Langer
Yuqi Zhang
Guojun Chen
Jinqiang Wang
Anna R Kahkoska
Jicheng Yu
Zhen Gu
Yanqi Ye
John B Buse
Weiwei Mao
Journal: Nature biomedical engineering (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Glucose-responsive insulin delivery systems; pancreatic endocrine function; β-cell function; transdermal patch; microneedles
Affiliations: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA., Zenomics Inc., Los Angeles, CA, USA., Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA., California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA., Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA., Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Department of Anesthesiology, Boston Children's Hospital, Boston, MA, USA., Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA., Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA. ., Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA. ., California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA. ., Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. ., Center for Minimally Invasive Therapeutics, University of California, Los Angeles, Los Angeles, CA, USA. .

Abstract:  Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsive behaviour typically have limited insulin-loading capacities and cannot be manufactured easily. Here, we show that a single removable transdermal patch, bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix, and fabricated via in situ photopolymerization, regulated blood glucose in insulin-deficient diabetic mice and minipigs (for minipigs &gt;25 kg, glucose regulation lasted &gt;20 h with patches of ~5 cm2). Under hyperglycaemic conditions, phenylboronic acid units within the polymeric matrix reversibly form glucose-boronate complexes that-owing to their increased negative charge-induce the swelling of the polymeric matrix and weaken the electrostatic interactions between the negatively charged insulin and polymers, promoting the rapid release of insulin. This proof-of-concept demonstration may aid the development of other translational stimuli-responsive microneedle patches for drug delivery. 

Retracted: No

PubPeer comments:
 I am a person with T1D and I found the data on Figure 4 unlikely. The CGM data gave constantly low glucose values (40 mg dl). Those poor minipigs must have severe hypoglycemia; yet, it was stated as normoglycemia. This cannot be correct. , 
 #1 Normal pigs have glucoses below the level of detection of the CGM device (50 mg dl). The pigs were happy and healthy. This is the wrong animal model to really make assessments of hypoglycemia as their fasting glucose is quite often less than 50. ,