Smart dual-responsive poly(2-hydroxyethyl methacrylate)/phenylboronic acid systems for diabetes management: role of molecular weight in controlled insulin release

In the present study, a dual pH- and glucose-responsive polymer based on poly(2-hydroxyethyl methacrylate) functionalized with 4-carboxyphenylboronic acid (p(HEMA-CPBA)) is successfully synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization at three different degrees of polymerization: 20, 40, and 200 with narrow dispersities (Đ) of 1.15, 1.17, and 1.18, respectively. The p K a values of p(HEMA-CPBA) are measured ∼7.7, 7.9, and 8.0 using the titration method and 7.78, 7.97, and 8.17 using the spectral difference method. Glucose responsiveness is verified by particle size increase of the synthesized polymer upon increasing glucose concentration from 0 to 3 mg/mL due to glucose‑boronate complex formation. P(HEMA-CPBA) is further evaluated for insulin encapsulation efficiency to release it in response to glucose concentration. Insulin encapsulation efficiencies are 76.2, 69.7, and 58.7 % for HP20, HP40, and HP200 with corresponding loading capacities of 19.3, 17.5, and 14.6 %, respectively. In vitro release studies at pH 7.4 show glucose-dependent insulin release, with HP40 achieving up to 65 % cumulative release at 3 mg/mL glucose. The synthesized polymers show ∼90 % cell viability for HFF-2 cells, showing low toxicity. Fluorescence microscopy confirms preserved cell morphology showing p(HEMA-CPBA) as biocompatible platform for diabetic treatments.