The burst release of drugs limited the development of the thermo-responsive hydrogels based on poly N-isopropylacrylamide (NIPAAm) for application in drug delivery systems. To overcome this problem, the drug sulfadimethoxine (SDMO) was conjugated via amide bond to the PNIPAAm hydrogel instead of loaded into the system. Therefore, SDMO was modified using maleic anhydride to get N-maleyl sulfadimethoxine (NMSDMO) and then utilized that to synthesize the sulfadimethoxine-conjugated PNIPAAm hydrogel (P[NIPAAm-co-NMSDMO]). The resultant monomer was then grafted into the hydrogel network at different weight percentage through radical polymerization. The NMSDMO monomer and the P[NIPAAm-co-NMSDMO] hydrogels were fully investigated. The in vitro drug released displayed sustained release in pH 5 and 7.4 for 24 h. Hydrolysis of the amide bond causes the release rate and total amount of drug to be greatest at pH 5, as compared to pH 7.4. As a result, the P[NIPAAm-co-NMSDMO] hydrogel was an effective sustained drug delivery system.
