A series of amphiphilic double-brush polymers based on itaconate diesters were synthesized with the objective of tailoring the thermal and mechanical properties of hydrogels formed by them; the amphiphilic itaconate diesters carried an MPEG350 segment and an alkyl chain, whose length was varied from C12 to C18. As was reported by us earlier (Macromolecules 2017, 50, 5004), the formation of the hydrogel was due to the crystallization of alkyl segments, as confirmed by the match of the rheological gel-to-sol transition with that of differential scanning calorimetry melting transition of the gel. In an effort to fine-tune the hydrogel-melting temperature and its strength, we varied the length of the alkyl chain length while keeping the hydrophilic segment length constant at MPEG350; apart from varying the alkyl chain length, an oxyethylene spacer was incorporated to examine the effect of decoupling the alkyl side-chain crystallization from the backbone. With these modifications, the melting temperature of the hydrogel was varied from 30 to 56 °C. Likewise, the strength of the hydrogel, as reflected by its storage modulus, varied from around 220 to 970 Pa; the softer gels typically exhibited a slightly larger critical shear strain beyond which the gel transformed into a sol. The thermal and shear-induced gel-to-sol transitions were reversible; however, the modulus after the shear-induced transition did not fully recover instantly (∼80%), suggesting that the formation of the extended gel network is slow. Further fine-tuning could be achieved by copolymerization of two different amphiphilic itaconate monomers, namely, those with C16 and C18, which provided an intermediate gel-melting temperature; however, co-gelation of the two preformed homopolymer gels yielded two distinct gel-melting transitions. Thus, this class of tuneable stimuli-responsive polymeric hydrogels prepared from biobenign components, namely, itaconic acid, 1-alkanols, and MPEGs, could serve as potential candidates for biomedical applications.

Diabetic patients need to take multiple insulin injections in a day to achieve efficient glycemic control. However, repeated injections can cause pain and discomfort for patients. Therefore, we have developed an amphiphilic double‐brush polymer‐based hydrogel (DBP‐hydrogel) that can encapsulate insulin and can be injected subcutaneously. Additionally, we have demonstrated the robust nature of DBP‐hydrogel by encapsulating small molecular drugs and large biological agents. Using a streptozotocin‐induced type 1 diabetic mouse model, we have demonstrated that a single injection of the insulin‐loaded hydrogel can efficiently control hyperglycemia for 24 hours, whereas 5 repeated injections of free‐insulin (commercial formulations) are required to achieve a similar level of glycemic control. This novel DBP‐hydrogel can stabilize encapsulated insulin without losing its activity for at least 90 days, which may have a huge impact in avoiding cold chain supply. Furthermore, a series of in vitro and in vivo experiments suggest that newly developed DBP‐hydrogel is highly biocompatible and does not cause immune response and inflammation.

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