The Effect Of A Biodegradable Paclitaxel-eluting Stent On Bile Duct Healing After Trauma In Porcine Model

Part 1Developing a new synthetic polymers as the covering materials forstent and manufacturing a novel biodegradable paclitaxel-elutingbiliary polylactide stent with this polymersObjective To manufacture a novel biodegradable paclitaxel-eluting biliary polylactidestent.And a new synthetic polymers was developed as the covering materials for thisstent.Methods With the help of institute of polymer science of Zhejiang University,a newsynthetic polymers called elastic body was synthesized with L-LA andε-CL as thecovering material.Paclitaxel in a powder form can be easily mixed in with thetetrahydrofuran(THF)solution,which is used as a solvent for elastic body.Thebiodegradable biliary polylactide stent was dipped in a container filled withelastomer-paclitaxel liquid,and heat dried whereafter.Result A new synthetic polymers was developed as the covering materials for thebiodegradable paclitaxel-eluting biliary polylactide stent.Conclusion A novel biodegradable paclitaxel-eluting biliary polylactide stent was manufactured.Part 2The drug release in vitro for biodegradable paclitaxel-elutingbiliary polylactide stent measured by HPLCObjective To investigate the efficacy of drug release for biodegradablepaclitaxel-eluting biliary polylactide stent by HPLC.Methods The biodegradable paclitaxel-eluting biliary polylactide stent was placed inphosphate buffered saline solution for 4 weeks.3 ml of phosphate-buffered solution waschanged daily and the daily amount of paclitaxel released was measured byhigh-performance liquid chromatography.The extraction was performed with DCM.Theoragnic layer was evaporated and the residual was reconstituted with mobile phase.Theconcentration of paclitaxel was assayed on a C18 column with a mobile phaseconsisting of methanol-acetonnitrile-water(58:37:5)at a flow rate of 1 ml/min anddetected at 230nm.Result A linearity was obstained from 0.1 to 30ug/ml of paclitaxel in plasma with agood correlation(r=0.9999,n=7).The intra-day and interday validations were 4.65 %,1.63 %,1.19 % and 4.65 %,2.03 %,1.51%,respectively.And the mean recoverieswere 95.54 %,98.61% and 96.36 % for low,middle and high checksamples,respectively(0.4,2.5,25ug/ml).The total amount ofpaclitaxel released was about281 ug(30.4 %)over a month as determined with in vitro drug delivery kinetics.Conclusion The improved method was a sensitive,reproducible and simpleassay.And the overall release rates of biodegradable paclitaxel-eluting biliarypolylactide stent were extremely slow and persistent. Part 3The effect of a biodegradable paclitaxel-eluting biliary polylactidestent on anastomic wound healing of the common bile duct inporcine modelObjective To evaluate the effect of a biodegradable paclitaxel-eluting biliarypolylactide stent on bile duct scar formation and biliary stricture by observing thehealing process after stent placement in a porcine billiary model.Methods A porcine bile duct injury model was construced.Thirty swines wererandomly divided into two groups in this experiment(experimental group and contronlgroup).Biodegradable paclitaxel-eluting stent were surgically inserted in the bile ductof fifteen swines in experimental group while biodegradable stent without paclitaxelwere placed in rest fifteen swines of control group.Animals were sacrificed 1,3 or 6months after operation.The anastomic wound healing of the common bile duct wasobserved.Bursting pressure and diameter of anastomosis were measured and comparedbetween the two groups.The status of scar formation,cholangiohraphy,histologicfoundings by HE,Masson staining and electron microscope were evaluated.And theexpression ofα-SMA,TGF-β1 and TGF-β1 mRNA were also performed and compared.Result All operation were accomplish successfully.There is no death in or afteroperation.No obvious leakage happened in either experimental or control group.Bursting pressure showed no difference between two group.The diameter of anastomosisin the experimental group was significantly larger than that in control group either 3 or6 months after operaion.group,Histologic examination and electron microscope resultsshowed inflammatory reaction and hyperplasia of the bile duct wall in the paclitaxelgroup was much more moderate than that in control group.And the expression of α-SMA,TGF-β1 and TGF-β1 mRNA in the paclitaxel group was less than that in controlgroup,and the difference becomes significantly 3 and 6 months after operation.Conclusion Local delivery of paclitaxel via a biodegradable stent has the potential torelieve the billiary stricture in porcine model and have no obvious negative influence onanastomic wound healing of the common bile duct.