Preparation of keratin hydrogel/hydroxyapatite composite and its evaluation as a controlled drug release carrier

• Carboxymethyl (CM) keratin was prepared by the reaction with iodoacetic acid.
• Keratin and CM-keratin formed hydrogels in 0.5 M CaCl2.
• CM-keratin hydrogels conjugated with hydroxyapatite (HA) in simulated body fluids.
• More HA accumulated on CM-keratin hydrogel than on keratin hydrogel.
• HA conjugates of CM-keratin hydrogel showed sustained release of salicylic acid.

Infection after artificial joint replacement is a serious problem, which requires the re-implantation of prosthesis. To aim at developing bone filling materials having both osteoconductivity and ability as a sustained drug release carrier, composites of wool keratin or carboxymethylated (CM) keratin hydrogels with hydroxyapatite were prepared and evaluated as a sustained drug release carrier. CM-keratin was prepared by the reaction of keratin extracted from wool with iodoacetic acid. Hydrogels were obtained by dropping keratin or CM-keratin solution into CaCl2 solution. The composites were obtained by immersing hydrogels in simulated body fluid (SBF). The introduction of carboxymethyl groups to keratin facilitated the deposition of hydroxyapatite on hydrogel. After 7 days of immersion in SBF, a 4–5 times higher amount of hydroxyapatite was accumulated on CM-keratin hydrogel than that on keratin hydrogel. When salicylic acid was loaded on keratin and CM-keratin hydrogels, a good sustained release was observed; that is, 90% of a drug was released up to 14 days after 60 and 45% of the initial burst in 1 day. On the other hand, initial release within 1 day was suppressed by forming a composite with hydroxyapatite and the release was almost ceased at 3 days when 60% of the drug was released.Although further improvement to prolong drug release might be necessary, CaKHA and CaCMKHA are expected to be a promising novel type of bone filling materials which has both osteoconductivity and sustained drug release ability.