A Glucose‐Responsive Polymer Nanocarrier Based on Sulfonated Resorcinarene for Controlled Insulin Delivery

Abstract

A nanocarrier (p(6SRA‐5B)) for glucose‐controlled insulin delivery consists of sulfonated resorcinarenes (SRA) that are assembled into a spherical shell and are attached to each other with phenylboronate linkers. p(6SRA‐5B) is stable in water and blood plasma at normal glucose concentrations. At high glucose levels (>5 mM), p(6SRA‐5B) dissociates into SRA and phenylboronates through competitive interaction with excess glucose. Insulin was successfully encapsulated into the cavity of p(6SRA‐5B) and its release was investigated in water and blood plasma by NMR, UV, CD, and fluorescence spectroscopy. The results show that the dissociation of the nanocarrier and the insulin release occurs with an increase in glucose concentration. At 5 mM glucose, the nanocarrier is stable, and the insulin release does not exceed 10 %. Increasing the glucose concentration to 7.5–10 mM results in a 40–100 % insulin release. p(6SRA‐5B) is thus a promising insulin nanocarrier for the treatment of type 1 diabetes.

Insulin Delivery Using Dynamic Covalent Boronic Acid/Ester‐Controlled Release

“…[ 173 ] The authors hypothesised that this could be achieved through optimisation of the sulfonated resorcinarene ( 35 ) to phenylboronic acid ( 36 ) ratio during the preparation of their nanoparticles ( Scheme ). [ 174 ] Experiments proved this hypothesis to be true, with a 6:5 molar ratio of sulfonated resorcinarene to phenylboronic acid proving to be optimal. Nanospheres of that composition were capable of insulin encapsulation with 76% efficiency, and their loading capacity was determined to be 8.5%.…”

A Review of the Application of Resorcinarenes and SBA-15 in Drug Delivery

“…In the two previous studies, an important factor mentioned is that resorcinarenes are not toxic. In addition, because they possess a cavity, they can effectively encapsulate other molecules such as insulin and depending on the groups with which they are functionalized, they can become very soluble in water and in blood plasma at normal pH levels [49].…”

A glutathione responsive nanocarrier based on viologen resorcinarene cavitand and 1-allylthymine

“…resorcinarene derivatives which should greatly facilitate their excretion from the body. 14 Previously, applying the present approach, we obtained resorcinarene-based nanocarriers for glucose-induced insulin release 15 and for pH-controlled delivery of the anticancer agent doxorubicin to cancer cells. 16 Both nanocarriers exhibit high stability, strong drug binding and rapid release during critical physiological changes, namely, elevated glucose levels (for insulin delivery) and decreased pH (for doxorubicin delivery).…”