BACKGROUND: Chitosan microspheres are widely used in various drug sustained release systems because of their good biocompatibility and antibacterial activity.
OBJECTIVE: To study the preparation and release in vivo of isoniazid-chitosan microsphere-loaded human allogeneic bone.
METHODS: After the preparation of the isoniazid-chitosan microspheres (ICMs) by spray-drying process, a 45-day in vitro drug release experiment was carried out. Isoniazid-loaded human allogeneic bone grafts (control group) and ICMs-loaded human allogeneic bone grafts (experimental group) were respectively implanted into both sides of the iliac in rabbits. The drug release characteristics in vivo were determined by high efficiency liquid chromatography.
RESULTS AND CONCLUSION: The appearances of ICMs were round, smooth and well-dispersed. Their average diameter and drug-loading rate were (3.33±0.9) μm and (16.25±1.24)% respectively. There was no burst release in vitro. The release quantity was about 20% of total amount at 24 hours, and about 76% at 45 days. The release curve was flat. The drug release was stable. Mathematical model was in line with Ritger-Peppas model. In the experimental group, the concentration of isoniazid was slowly increased at first 28 days, and then slowly decreased and lasted for more than 56 days in vivo. The concentration range was 38.05-155.75 µg/g. In the control group, the isoniazid concentration reached a peak 1982.5 ug/g in about 1 week, and the isoniazid could not be detected around the bone after 21 days. The ICMs have the characteristics of slow isoniazid releasing both in vitro and in vivo, and the release can last for a long time. ICMs-loaded bone can be used as an implanted material, which can provide mechanical support and long time local chemotherapy after the operation of bone tuberculosis.