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

Abstract

Polyamine–salt aggregates (PSA) are biomimetic soft materials that have attracted great attention due to their straightforward fabrication methods, high drug‐loading efficiencies, and attractive properties for pH‐triggered release. Herein, a simple and fast multicomponent self‐assembly process was used to construct cross‐linked poly(allylamine hydrochloride)/phosphate PSAs (hydrodynamic diameter of 360 nm) containing glucose oxidase enzyme, as a glucose‐responsive element, and human recombinant insulin, as a therapeutic agent for the treatment of diabetes mellitus (GI‐PSA). The addition of increasing glucose concentrations promotes the release of insulin due to the disassembly of the GI‐PSAs triggered by the catalytic in situ formation of gluconic acid. Under normoglycemia, the GI‐PSA integrity remained intact for at least 24 h, whereas hyperglycemic conditions resulted in 100 % cargo release after 4 h of glucose addition. This entirely supramolecular strategy presents great potential for the construction of smart glucose‐responsive delivery nanocarriers.

Polyelectrolyte-multivalent molecule complexes: physicochemical properties and applications

“…13a). 164 Under hyperglycemic conditions (10, 15 and 20 mM glucose), an acidic environment is produced, which leads to the protonation of phosphates (valency reduction) and activates the PEMMCs disassembly. As a consequence, all insulin peptides are released whenever glucose overcomes a threshold concentration (Fig.…”

Progress in the preparation and evaluation of glucose-sensitive microneedle systems and their blood glucose regulation

“…As shown in Fig. 6(b), Omar Azzaroni et al 61 prepared a cross-linked polymer network with positively charged amino groups, and simultaneously loaded insulin and glucose oxidase. The local acidic microenvironment caused amino protonation in the polymer segment, which destroyed the previously tight cross-linking network, thus realizing the glucose-sensitive release of insulin.…”

Phase Behavior and Electrochemical Properties of Highly Asymmetric Redox Coacervates

“…Polyamine-phosphate colloids have been proposed as nanocarriers for drug delivery. 18,35 Coacervates based on charged bio-macromolecules (mostly polylysine, polyarginine, and nucleic acids) and a wide variety of bioactive multivalent ions (such as ATP and other metabolites) have been reported, opening an avenue to the design of bioactive colloidal aggregates. 36,37 In this context, a series of coacervate materials were reported with capacity to be formed and to be dissolved by applying external stimuli, 19,38,39 to load biomolecules, 35 and even to serve as nanoreactors for biologically relevant reactions.…”