We prepared keratin nanoparticles, which could respond to temperature and pH changes and to redox reactions, by electrostatic association of keratin and a cationic surfactant, dioctadecyl dimethyl ammonium chloride (DODAC). Solubilized keratin chains were assembled into nanoparticles (Ker-DODAC) and then crosslinked by disulfide formation. The resultant nanoparticles (Ker-DODACss) possessed a hydrophobic core composed of DODAC, enabling hydrophobic compounds to be loaed and retained in the core. By increasing the temperature, the fluidity of the core was increased, resulting in Ker-DODACss swelling and burst release of loaded compounds. Next, cholesterol was loaded into Ker-DODACss to modify the inner environment, such as the hydrophobicity and fluidity of the core. The nanoparticles (Ker-DODACss-Chol) exhibited reduced fluidity of the core and suppressed release of the payload. Furthermore, the release could be triggered by decreasing the electrostatic interaction between keratin and DODAC at pH values lower than 7.4. It was also found that Ker-DODACss-Chol possessed the ability to release payloads by breaking disulfide bonds. As a further internal modification, we incorporated a lipophilic antioxidant, α-tocopherol, into Ker-DODACss-Chol. It was confirmed that Ker-DODACss-Chol could act as a physical barrier to prevent α-tocopherol from undergoing oxidative degradation.
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