Study On Biocompatibility And Pharmacokinetics Of Dextran-magnetic LDH-Fluorouracil Transshipment Model

1Study on acute toxicity experiment of the Dxtran-Magnetic LDH-Fluorouracil drug deliverysystemTo measure the acute toxicity level of “Dextran-Magnetic LDH-Fluorouracil deliverymodel （DMF）, Dextran-Magnetic LDH compound （DM） and Magnetic carries MLDH.Afterdosing intervention with irrigation stomach and peritoneal injection, the activities and deathcondition of mice were observed in three days, and the simple probability until method was tocalculate the LD50of DMF, DM and MLDH. No obvious acute toxicology appeared in thegroups of irrigation stomach group, and the LD50in peritoneal injection group were2542.8,3279.5and1951.0mg·kg^-1,respectively for DMF, DM and MLDH. The drug delivery systemof DMF was provided with low toxicity, and a better biocompatibility. Modify with Dextrancould significantly reduce the toxicity levels of magnetic carriers MLDH.2Study on the bound ratio of bovine serum albumin to5-Fluorouracil loaded by a“dextran-magnetic LDH-Fluorouracil” transfer modelTo determine the binding ratio of bovine serum albumin to5-Fluorouracil loaded by thedelivery model of Dextran-Magnetic LDH-Fluorouracil （DMF）, and evaluate the convertingin binding parameters of5-FU to bovine serum albumin. The concentration of5-FU wasdetermined by HPLC internal rat method, and the binding ratio of5-FU to bovine serum albumin was assayed with a method of equilibrium dialysis within bag membrane. Thebinding ratio of5-FU in original and DMF delivery model to bovine serum albumin were21.8⁷.03%and15.3³.60%, respectively. The bound parameters Kpin original model andDMF delivery model were58.97L·mmol^-1and47.33L·mmol^-1, the binding site n were0.057and0.043, the apparent binding force constant βpwere0.91μmol·g^-1and0.80μmol·g^-1,and the dissociation constant Kdpwere18.32μmol·L^-1and32.31μmol·L^-1,respectively. Underthe DMF model, the binding ratio of5-FU to bovine serum albumin was significantly lower,and the bound constant decreased but the dissociation parameter of protein conjugatesincreased, which should be favorable for raising the unbound state concentration of5-FU inplasma.3Study on dissolution of Dextran-Magnetic LDH-Fluorouracil drug delivery model and theirin vitro-in vivo correlation.To compare the relative bioavailability and the correlation study on Dextran-MagneticLDH-fluorouracil （DMF） between in vitro and in vivo. In vitro dissolution dates of DMF werecollected for6hours. Plasma concentration date were obtained from rabbits after peritonealinjection DMF and5-FU with a single dose of660mg kg^-1. The plasma concentration of5-FU was assayed by HPLC and pharmacokinetic parameters were calculated with DAS2.0by computer. The level B model was assessed by comparing in vitro dissolution time（MDT）and in vivo dissolution time（MRT）.Concentration-time curves of DMF and5-FU totwo-compartment open model. The t_maxwas （2.580±0.030） h and （0.225±0.030） hrespectively; The C_maxwas （6.301±0.666） mg L^-1and （24.58±1.297） mg L^-1; AUC（0-t）was （19.75±1.365） mg L^-1·h and （57.82±6.976） mg L^-1·h;5-Fluorouracil was used reference tostudy the pharmacokinetics of DMF in vivo, t_maxand t1/2were prolonged, C_maxwas reducedand bioavailability was raised. DMF has a higher bioavailability than5-FU. There was asignificant correlation between the dissolution in vitro （MDT） and the absorption in vivo（MRT） of DMF（R=0.9798）.