Characterization And Application Of Injectable Hydrogel Fabricated From Hyperbranched Poly(Amido Amine)

Injectable hydrogels have attracted a great many attentions in recent years. The injectable hydrogels are liquids or semi-solids with shear thinning property before being injected into the human body. However, they can quickly transform into solids with appropriate strength after injection. Functional injectable hydrogel is a hot spot in the current research. Nowadays, the self-healing hydrogels, fluorescent hydrogels and stimuli-responsive hydrogels have been reported. Nevertheless, there are only a few reports on multi-functional injectable hydrogels.Hyperbranched poly (amido amine) (HPAMAM-1) synthesized from methylene diacrylamide (MBA) and N-Aminoethylpiperazine (AEPZ) via Michael addition is a kind of polymer with highly branched structure. The other structural features include: lots of amine groups, which enable the HPAMAM to react with the active groups like aldehyde groups to form network; with large molecular cavity, favorable to the encapsulation of small molecular drugs or biopolymers and drug-release; able to emit fluorescence under UV irradiation at 300-400 nm; good solubility. In short, HPAMAM-1 is suitable in fabrication of multi-functional injectable hydrogels. Here in the first part of our work, we fabricated a kind of injectable hydrogel by HPAMAM-1 and oxidized alginate (OALG). This hydrgoel was formed by dynamic covalent bonds (acylhydrazone bonds)and dynamic non-covalent bonds (electrostatic interactions and hydrogen bonds) between the HPAMAM and OALG. Therefore, this hydrogel is able to self-heal, responsive to pH values, biodegradable, able to swell and release drugs. Moreover, this hydrogel is of good fluorescent property and injectability. In this work, we analyzed the microstructure and described the properties of the HPAMAM-1/OALG injectable hydrogels mentioned above in details.When physically mixing the small molecular drugs with the hydrogels, the drug may be released very quickly, which leads to some disadvantages like frequent dosing and relative high toxicity. If the drugs are chemically bonded onto the hydrogel, the sustained release time can be lasted longer. Therefore, the problems including frequent dosing and toxicity can thus be solved. In the second part of our work, we designed another injectable hydrogel based on HPAMAM. In this hydrogel, the model drug 5-fluorouracil is chemically bonded to the HPAMAM molecules, which effectively prolonged the release time and the release rate was more uniform. Different from the HPAMAM-1, the hyperbranched poly(amido amine) synthesized from N,N’-bis(acryloyl)cystamine, MBA and AEPZ via Michael addition reaction (HPAMAM-2) are of disulfide bonds on their backbones. The injectable hydrogel from HPAMAM-2 and OALG is of unique properties, including redox-responsibility and biological molecule sensitivity. In the second part of our work, we also analyzed the microstructures and illustrated the self-healing ability, pH sensitivity, biodegradability, swelling ability and drug release ability in details.