Construction And Evaluation Of Colon-targeted 10-Hydroxycamptothecine Lipidosome Macroporous Resin

HCPT(10-hydroxycamptothecine, HCPT) is endemic to China Gong Dong Kojo wood acuminata seeds isolated a natural alkaloid extracted. The HCPT liposomes prepared to make the lactone ring structure embedded in the bilayer lipid membrane. This prevents open-loop, so as to maintain its biological activity and increasing the solubility of the drug. However, the stability of liposomes is not good, because it can be easily destroyed in the gastrointestinal tract and is difficult to achieve the effect on slow release of colon rectal. In this study, the drug-containing liposomes contain macroporous resin D101, to make HCPT liposomes be solid and then coated by colorectal targeted material, to achieve more accurate targeting effect. It combines the advantage of solid liposome, macroporous resin and coating.That’s, to transmite drug-containing liposomes to the target organs,and then the HCPT liposomes release slowly,which combines liposomes and target organs’ s cytomembrane and delivery drugs to target organs to achieve the purpose of slow-release and targeted therapy.The study mainly contains the following contents:1. literature review. To summarize the progress of relative study of 10-hydroxycamptothecin,materials of colon targeted and drug delivery system of colon targeted and so on.2. To prepare HCPT liposomes by film- ultrasonic dispersion.Entrapment efficiency is taken as indexes.Through single factor,screening three main factors affecting liposome encapsulation efficiency : the ratio of drugs and D101,the ratio of phospholipid and concentration of cholesterol phospholipid,and through the optimization of the orthogonal screening.Use Sephadex G-50 gel chromatography-HPLC to measure liposome’s encapsulation efficiency. HCPT liposomes are eluted with p H3.5 acetate buffer liposomes, then measure the sample for analysis.Determinate HCPT encapsulation efficiency,to make encapsulation efficiency over 80%.3. Preparation of HCPT liposome containing in macroporous resin composite. Amount of residue is token as indexes,macroporous resin D101 as a carrier,and through adsorbing and gradual drying to macroporous resin D101 so that it can reach the purpose on HCPT liposomes soldifying and further to release slowly.Through single factor’s study,screening major factors:the amount of Tween-80, the amount of mannitol, Tween-80 to join the way. Through the optimization of the orthogonal screening of prescription,Use Sephadex G-50 gel chromatography-HPLC to measure liposome’s encapsulation efficiency and amount of residue.Base on formula,measure relative resualts.4. Coated HCPT liposome-D101. Release rate is token as index,Use emulsion solvent evaporation method,study the technology and prescription factors,Through the optimization of the orthogonal screening of prescription.In the preparation on techonology, selected three main factors: the curing temperature, curing time and stirring speed.On prescription factors,screened out three main factors: the ratio of the coating material and D101,dosage of DEP,dosage of PEG400.5. Evaluate on HCPT liposome-D101.It mainly include XRD and DSC;HCPT liposomes of macroporous resin external release experiments and release model is established in this pape Respectively.External release experiment:in artificial gastric juice(p H = 1.0), artificial intestinal fluid(p H = 6.8) and artificial colon solution(p H = 7.8) is carried out sequentially in artificial gastric juice 2h(1 ~ 2h), artificial small intestinal 3h(2 ~ 5h), artificial colonic fluid 7h(5 ~ 12h) were measured.Base on the resualts and formula,make the release curve and modeling.In the coating HCPT liposomes-D101 artificial colonic fluid,external release rate will be over 90%,to reach relative requirement.6. release experiments in vivo. 12 rats were randomly divided into three groups, namely: D101 containing free drug,uncoated drug-containing liposome,coated drug-containing liposomes macroporous resin. The rats given oral samples. Sampled at predetermined time points. Determination of drug concentration in each segment of the gastrointestinal tract by HPLC,investigate the distribution of the drug in various tissues.In coated drug-containing liposomes macroporous resin,make drugs in stomach and small intestine of rats hardly release,and begin to release the drug into the colon, to achieve the effect of colon releasing.The issue in the early pharmacodynamic evaluation is based on the use of modern technology to prepare for drug-containing liposomes macroporous resin, which is simple process, good feasibility. To study the in vitro release and in vivo drug release formulations behavior, Evaluate of the colon targeted release characteristics of the formulation. systematically.To explore novel drug delivery system,this trial provide a certain experimental basis,which is a useful exploration for the development HCPT, has great value on the development of application.