Biologically Inspired and Chemically Derived Methods for Glucose‐Responsive Insulin Therapy

Abstract

The controlled delivery of therapeutics in a manner responsive to physiological indicators has promise in realizing new therapeutic approaches to combat disease. This approach is especially relevant in the context of diabetes. Natural fluctuations in blood glucose seen in the healthy state, complete with peaks and troughs, are poorly regulated as a result of detrimental production or ineffective signaling of the insulin hormone. While several manifestations of diabetes are treated with regularly administered exogenous insulin, the present standard of care results in suboptimal glycemic management that poorly recreates natural hormone control, leading to long‐term instability and a significantly increased risk for secondary health complications. New synthetic technologies that make insulin available only when needed, and at the exact dose required, have been explored under the broad vision of realizing a “fully synthetic pancreas.” Yet, many challenges remain to realizing a technology that is appropriately responsive, safe, and well integrated into a manageable routine. Herein, many of the approaches explored thus far to sense physiological blood glucose and elicit response through the release of therapeutic insulin are summarized. The approaches point to a new, autonomous approach to managing diabetes with biomimetic therapy.

Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis

“…Lectin is a group of naturally glucose- and mannose-binding protein moieties. The most widely exploited molecule in this respect is Concanavalin A (Con A), a lectin family member which is capable of binding reversibly and specifically to glucose [ 180 ]. For example, Con A, grafted on glucosyloxyethyl methacrylate along with N,N′-methylene-bis-acrylamide (MBAAm), was used to fabricate glucose-responsive hydrogel [ 181 ].…”

Can nanoparticles and nano‒protein interactions bring a bright future for insulin delivery?

“…Typically, the glucose-responsive systems are based on glucose oxidase (GOD) 48 , and the first GOD-based pH sensitive hydrogel for glucose-responsive delivery of insulin was reported in 1984 49 . GOD is widely used for the quantification of blood glucose due to its high sensitivity in reaction with glucose.…”

Insulin Delivery from Glucose‐Responsive, Self‐Assembled, Polyamine Nanoparticles: Smart “Sense‐and‐Treat” Nanocarriers Made Easy

“…To evaluatet he glucose responsiveness, GI-PSAs were incubated at 37 8Ci ns olutionsw ith different glucose concentrations, including hyperglycemic levels (10,15, and 20 mm), [76] a normoglycemic level of 5mm, [77] and ac ontrol level of 0mm. We recordedt he time variation of pH and %T immediately after the addition of glucose( see Figure 3a and b, respectively).…”