Evaluation Of Anti-TB Drug Delivery Materials Locally Oriented In Rabbit

Tuberculosis has influenced people’s health and quality of life forlong time. In addition to the surrounding lymph nodes around outside thenucleus, bone and joint tuberculosis is the most common extrapulmonary tuberculosis, accounting for about3%of tuberculosis. Thetraditional oral anti-TB drugs is difficult to achieve the desired drugconcentration in the tumor region, because of bone and joint tuberculosislesions particularity and it is liable to lead to a series of side effects. Tosolve the problems, a method of local treatment of bone tuberculosis drugis introduced. People solve the spinal tuberculosis remove boneformation after multiple defects with autologous bone allograft bone andartificial bone as repair materials now. Autologous bone and allograftbone are unable to receive a large number of anti-tuberculosis drugs, sothe artificial bone is widely used as local sustained release carrier. PLGAhas advantages of larger drug loadings, long-term drug release,adjustable degradation time. The β-TCP has good biocompatibility, andbiodegradation. It can provide bone formation with elements such ascalcium during the degradation. The experiment is to join INH and RFPinto the PLGA and β-TCP materials, then observe its role in the repairof rabbit radial defect.1. Synthetic of INH-RFP-PLGA-β-TCP medicine slow release materialsWe dissolves PLGA in certain amount of1,4-2oxygen sulfur ring,and divided the appropriate solution average PLGA fully dissolved solutioninto four groups, according to the content of PLGA take correspondingβ-TCP. According to predetermined drug-polymer interactions take INHand RFP powder, four groups of solution, respectively are joined into the β-TCP, beta TCP and INH powder, beta TCP and RFP powder and betaTCP, INH and RFP powder. Ultrasonic blending, the suspension liquid isput into a mould, then is frozen for2hours at-4℃,-20℃and-80℃successively. Put the mould in the lyophilizer freeze and dry for72hours.2、The resulting material was frozen for later use. Rabbit for synthesizingof the distal radius bone defects and rabbit in vivo osteogenesis ability ofobservation.The fifty2.0~2.5kg of male New Zealand white rabbits were randomlydivided into five groups, each group of10rabbits. A length of10mm radialbone loss is made by surgical method PLGA-β-TCP, INH-PLGA-β-TCP,RFP-PLGA-β-TCP, and INH-RFP-PLGA-β-TCP are implanted into theradial bone defects and comparing non-implantable material of any controlgroup.12weeks later, through a general observation, means of imagingstudies, histological and biomechanical examination and histomorphometryof the material, such as osteogenesis the situation and determination of therelease of the local anti-TB drug with situation HPLC.The results showed that are assessed after12weeks, the control groupdid not achieve bone healing standard. Groups3,4and5have reached abone healing standard; The bone tissue of groups2、3、4and5has healed,while the control group showed a lot of fiber cells and fat cells;biomechanical examination the control group formed nonunion, with α=0.05standard, F value of1.11is less than3.24, and P value of0.37isgreater than0.05by groups2,3,4and5indicate that there is no significantdifferences between the experimental groups; histomorphometry standardsto α=0.05, F value of431.10is greater than3.24, P value is less than0.05description not identical between the groups, through follow-up pair wisecomparisons showed that the control group were significant between theexperimental group and the differences, no significant differences betweenthe groups3,4and5of section2. After4、8and12weeks，the drugconcentration in peripheral blood groups3,4and5were measured by high performance liquid chromatography，The results of4week showed that theconcentration of the three sets of blood INH is15.49±1.45μg·ml-1, theconcentration of the four sets of blood RFP is16.23±1.51μg·ml-1， thefifth group of blood concentrations of INH is15.54±1.47μg·ml-1and RFPis16.31±1.35μg·ml-1. The results of8week showed that the concentrationof the three sets of blood INH is5.49±0.52μg·ml-1, the concentration of thefour sets of blood RFP is6.48±0.58μg·ml-1， the fifth group of bloodconcentrations of INH is5.54±0.41μg·ml-1and RFP is6.26±0.46μg·ml-1.The results of12week showed that the concentration of the three sets oflocal blood INH is1.93±0.21μg·ml-1, the concentration of the four sets ofblood RFP is1.97±0.21μg·ml-1，the fifth group of blood concentrationsof INH is1.56±0.19μg·ml-1and RFP is2.26±0.23μg·ml-1. After12weeks,the method of high performance liquid chromatography by the local drugconcentration groups3,4and5were measured, The results showed thatthe concentration of the three sets of local INH is6.49±0.38μg·ml-1, theconcentration of the four sets of local RFP is6.65±0.42μg·ml-1， the fifthgroup of local concentrations of INH is6.54±0.45μg·ml-1and RFP is6.65±0.44μg·ml-1. The experiment shows that INH-RFP-PLGA-β-TCP ofthe material can well repair rabbit radial bone defects. The anti-TB drug inmaterials has no significant effect a radial defect repair. The anti-TB drugsin materials can release stably for a long time and keep bactericidalconcentration in the local part.