Study On Anti-tuberculosis Drug Sustained-release System By Hydrogel Encapsulation During Operation

The onset of spinal tuberculosis is hidden,and delayed diagnosis or improper treatment can lead to serious complications such as paraplegia and kyphosis.However,Systemic anti-tuberculosis chemotherapy has several disadvantages such as high liver and kidney toxicity and insufficient effective drug concentration in local lesions.Therefore,the development of local drug delivery systems based on artificial bone scaffold materials has become an important research direction for spinal tuberculosis.Different from constructing a drug delivery system in vitro before surgery,we have developed an immediate intraoperative encapsulation technology by physically dissolving the first-line chemotherapy drugs,isoniazid(INH)and rifampicin(RFP)as well as osteogenic growth peptide(OGP)to prepare a mixed drug solution.Then the tricalcium phosphate(TCP)porous artificial bone scaffold was immersed in the drug solution to obtain drug-loaded scaffold(TCP-drugs).Finally,the drug-loaded scaffold was immersed in chitosan/β-glycerophosphate(CS/β-GP)temperature-sensitive hydrogel.After vacuum adsorption,it is heated at 80 ℃ for 40 minutes to realize the rapid in-situ gelation of the CS/β-GP temperature-sensitive hydrogel in the pores of the drug-loaded scaffold.In this way,the anti-tuberculosis drug sustained-release system(TCP-drugs(?)CS/β-GP)was coated hydrogel layer.In vitro drug release experiments show that the encapsulation of hydrogel can inhibit the explosive release of drugs in the initial release period,and can maintain sustained drug release for a long time in vitro(INH,158 days;RFP,53 days)and effective drug concentration always higher than the minimum inhibitory concentration(MIC).In vitro antibacterial experiments and cytotoxicity experiments show that the TCP-drugs(?)CS/β-GP sustained-release system can effectively inhibit the growth of Mycobacterium tuberculosis,and the hydrogel encapsulation reduces the cytotoxicity of INH and RFP.In addition,the system can effectively repair bone defects caused by Mycobacterium tuberculosis infection and inhibit local inflammation in vivo.The implant has no obvious liver and kidney toxicity.It is superior to our previous drug delivery system(TCP-drugs@PVA)prepared in vitro.This study introduces an encapsulation technology constructed in situ by instant hydrogelation during surgery,which shows an effective anti-tuberculosis effect on bones and joints.The instant hydrogelation in the encapsulation technology can adjust the type and dosage of the drug and the ratio of chitosan and β-glycerol sodium phosphate at any time during the operation according to the condition of the disease to achieve the best drug release effect.