可塑性纳米-羟基磷灰石/聚β-羟基丁酸与戊酸酯-聚乙二醇-庆大霉素药物释放系统的生物相容性及安全性

Biocompatibility and security of the plastic nano-hydroxyapatite/poly(beta-hydroxybutyrate- co-beta-hydroxyvalerate)-polyethylene glycol- gentamicin drug delivery system

BACKGROUND: Gentamicin bead chain is an effective drug delivery system for treatment of osteomyelitis, but it cannot be degraded, need to be removed by second operation, and can breed pathogens. As a result, biodegradable drug delivery systems become a hotspot. Nano- hydroxyapatite/poly(β-hydroxybutyrate-co-β-hydroxyvalerate)-polyethylene glycol-gentamicin (nano-HA/PHBV-PEG-GM-DDS) is considered to be a good choice for the current predicament.OBJECTIVE: To evaluate the acute or chronic toxic reactions of the whole body and local tissues, intracutaneous stimulation, cytotoxicity and hemolytic reactions after bone remodeling and implantation of nano-HA/PHBV-PEG-GM-DDS, thus providing a new kind of material for treating osteomyelitis.METHODS: Plastic nano-HA/PHBV-PEG-GM-DDS was prepared using plastic fibrin glue as microsphere scaffold and nano-HA as the core carrier of GM that was coated with PHBV and PEG. The acute, subacute/chronic toxicity, implantation, hemolysis, cytotoxicity and intracutaneous stimulation tests were performed according to the evaluated criteria of medical implanted materials as well as biological and animal trials recommended in GB/T16886.1-1997.RESULTS AND CONCLUSION: The plastic nano-HA/PHBV-PEG-GM-DDS was nontoxic and caused no apparent changes in liver and kidney function and serum biochemical indexes. Pathological examination showed that the implanted material was covered with tissues, and inflammation changes accorded with the general regularity of inflammatory outcomes. After implantation, the nano-HA/PHBV-PEG-GM-DDS was biodegraded and replaced by osseous tissues. The hemolytic rate of the material extract to the composite diffusion solution was 1.2%, which was below the standard criteria (5%). Human bone marrow cells cultured in vitro with the plastic nano-HA/PHBV-PEG-GM-DDS grew normally with good morphology. There was no stimulation reaction according to the criteria after the diffusion solution was subcutaneously injected into the back of the animal. These findings indicate that the plastic nano-HA/PHBV-PEG-GM-DDS for treating osteomyelitis possesses excellent biocompatibility and security.