Hydroxyapatite/alginate/polyvinyl alcohol/agar composite double-network hydrogels as injectable drug delivery microspheres

An injectable and biodegradable drug delivery system to release antibiotics at a controllable rate to treat anti-bone infection was prepared. The system was based on nanocomposites of hydroxyapatite nanoparticles (HAP) and double-network hydrogels of sodium alginate (SA)/polyvinyl alcohol (PVA) prepared in the form of microspheres embedded in injectable agar gel. The double-network hydrogels of SA/PVA were prepared by sequential crosslinking of sodium alginate with calcium ions and then PVA by freeze-thawing method. The agar gel was used as a thermos-reversible gel to facilitate injection of microspheres. The characteristics of microspheres were analyzed by FTIR, XRD, SEM and water swelling. The drug release rate of the microspheres was measured at various compositions of the delivery system components. The results showed that increase in PVA content of hydrogels led to a tighter double-network which consequently reduced the drug release rate. Loading of the drug into HAP nanoparticles as drug nano-containers, prolonged the drug release time from 1 to 6 days when the content of HAP nanoparticles was within the range of 2.5 to 5%. The antibacterial activities of the drug-loaded composite hydrogels were evaluated against E. coli bacteria by disk diffusion tests showing anti-bacterial effectiveness of such drug delivery systems.