Variable swelling behavior of and drug encapsulation in a maleimide-modified hyaluronic acid nanogel-based hydrogel

Hyaluronic acid (HA) has garnered much attention in the development of novel hydrogels. Hydrogels, as drug delivery systems, are very important in tissue engineering applications. In this study, we developed a novel HA nanogel containing a cholesterol and maleimide derivative (HAMICH) and its corresponding crosslinked hydrogel (HAMICH gel) to encapsulate drugs for their subsequent release. HAMICH gels self-assemble into nanoparticles via hydrophobic interactions. Dynamic light scattering analysis of HAMICH revealed that the particle size tended to decrease with increasing degree of cholesterol moiety substitution. The HAMICH gel was prepared through a Michael addition reaction between HAMICH and pentaerythritol tetra(mercaptoethyl)polyoxyethylene. The concentration of HAMICH needed for gelation depends on the degree of cholesterol moiety substitution; the higher the substitution degree is, the greater the concentration of HAMICH needed. The HAMICH gel exhibited less swelling and a smaller volume change than the gel with an unmodified cholesterol moiety in phosphate-buffered saline (pH 7.4). The HAMICH gel displayed enhanced peptide and protein trapping abilities without hydrogel swelling, suggesting its potential as a HA hydrogel for biomedical applications. Hydrogels have attracted considerable attention in the biomedical applications because of their high functionalities, biocompatibility and biodegradability. This study on the novel hyaluronic acid (HA) nanogel-based hydrogel comprising HA modified with cholesterol derivatives and maleimide crosslinking groups. Depending on the degree of cholesterol derivative substitution, the properties such as water uptake, gelation behavior and protein encapsulation was investigated. The results suggested that the hydrogels enhanced peptide and protein trapping abilities have potential as a new hyaluronan hydrogel for biomedical applications.