High efficiency of in-situ cross-linking and acid triggered drug delivery by introducing tobramycin into injectable and biodegradable hydrogels

Abstract

High efficiency of in-situ cross-linking and acid triggered drug delivery is realized by introducing tobramycin into the hydrogels. Injectable and biodegradable hydrogels are prepared through two steps: First generation of reactive aldehyde groups in the sodium alginate (A-Alg) and then introduction of antibiotic tobramycin as cross-linker. Due to the formation of dynamic Schiff base bonds between the amino groups in tobramycin and aldehyde groups in A-Alg, the gelation of hydrogels can be realized immediately. Thus, tobramycin acts well as the first role cross-linker and the hydrogels containing tobramycin can be injected into the wound during the treatment. In addition, the acid from the decomposition of organic compounds by the bacteria can break the cross-linking points previously formed by tobramycin in the hydrogels. Therefore, tobramycin can be released and act as the second role model drug to kill the bacteria. Because the hydrogels network is broken, the release of tobramycin is more efficient than the traditional drug delivery from hydrogels by diffusion. Based on these unique properties, the present hydrogels containing tobramycin exhibit a good injectable and biodegradable capability. In addition, due to the existence of the reversible acid-labile linkages in the hydrogels, the hydrogels containing tobramycin are also self-healing, which additionally is favorable for the application of wound dressing. More importantly, the antibacterial hydrogels also demonstrate good biocompatibility in vitro and significantly therapeutic effects on an infected mice model in vivo. Based on the above special properties, the hydrogels cross-linked by tobramycin indicate a new approach to prepare hydrogel dressings with low-cost, non-toxicity and good anti-bacterial performance in the treatment of infectious wounds.