喃氟啶脂质体在荷瘤小鼠体内的分布

本文考察了喃氟啶脂质体在荷瘤小鼠体内的分布。选用了接种S_(180)肉瘤的小鼠,用高效液相色谱法测定各组织中的含药量。实验结果表明,喃氟啶脂质体在肿瘤部位的分布高于其它组织,而文献报道喃氟啶原药在肾脏的分布高于肿瘤部位,提示了喃氟啶制成脂质体后对靶区有更大的亲和力。     

用差示扫描量热法及激光拉曼光谱研究足叶乙甙对二棕榈酰磷脂酰胆碱脂质体膜流动性影响

本文用DSC和激光拉曼光谱研究抗癌药物足叶乙甙(4-去甲基表鬼臼毒素-β-D-乙叉吡喃葡萄糖甙,简称VP 16-213)与二棕榈酰磷脂酰胆碱(DPPC)脂质体的作用。VP 16-213分子掺入DPPC脂质体双层中,不但使相转变温度向高温移动,而且吸热峰的半高宽度随VP 16-213浓度增加而变宽。其Raman光谱在频率2850 cm~(-1)处的C-H键对称伸缩振动亦随着药物浓度增加而减弱。这些结果表明VP 16-213分子是定域在脂双层中DPPC分子链的C_1～C_9亚甲基区域,使脂质体的有序性提高而流动性降低。     

溴氰菊酯对脂质体流动性影响的质子核磁共振研究

本文用质子核磁共振(~1H NMR)技术研究了溴氰菊醋对二豆蔻酰磷脂酰胆碱(DMPC)、二棕榈酰磷脂酰胆碱(DPPC)和二硬脂酰磷脂酯胆碱(DSPC)脂质体流动性的影响。结果表明,溴氰菊酯增加这三种脂质体的流动性。     

正交试验优化硫酸长春新碱脂质体的制备工艺

目的制备性质稳定的硫酸长春新碱脂质体。方法采用单因素试验考察磷脂与胆固醇比例、药脂比、脂质浓度、载药温度、载药时间、外水相p H值对硫酸长春新碱脂质体包封率的影响。以包封率为指标,分别以氢化磷脂(SPC-3)和二硬脂酰磷脂酰胆碱(DSPC)为磷脂材料,通过正交试验考察载药温度、药脂比和载药时间对制备工艺的影响,优化出硫酸长春新碱脂质体的最佳制备工艺。结果硫酸长春新碱脂质体的最佳制备工艺为:将药物溶液(按照药物含量计)和空白脂质体溶液(按照脂质含量计)按照1∶20的比例混合,用Na2HPO4直接调节外水相p H值至7.2。SPC-3脂质体在65℃条件下载药,载药时间30 min。DSPC脂质体在60℃条件下载药,载药时间10 min。结论优选出的硫酸长春新碱脂质体的处方工艺稳定可行。     

喃氟啶从Poloxamer407凝胶基质中的体外释放

目的:观察Poloxamer 407凝胶的形成及液体/凝胶互相转化的条件和喃氟啶在该凝胶中的体外释放.方法:以磷酸盐缓冲液[pH(7.40±0.01)作为Poloxamer 407的稀释剂,以喃氟啶作为实验药物做体外溶出.结果:Poloxmer 407的浓度在15%～40%之内时,随着温度从0℃上升到37℃,其混合物从液体迅速转化成凝胶.相变温度随着Poloxamer407的浓度升高而降低.喃氟啶在该凝胶中的体外释放为零级释放,且随Poloxamer 407浓度的增加,释放速度变慢.8h时.含Poloxamer 407分别为20%,25%,30%,35%(m/m)的凝胶中时喃氟啶的累积释放率分别是(98.22±0.12)%,(86.20±0.20)%,(68.25±0.14)%,(50.02±0.08)%.结论:鉴于Poloxamr 407所具有的特殊的逆温相变性质,作为血管外注射型缓释植入剂的载体是有前途的.     

主动靶向脂质体的相变温度与靶细胞摄取的相关性研究

分别采用二硬脂酰磷脂酰胆碱(DSPC)、氢化大豆磷脂(HSPC)、二棕榈酰磷脂酰胆碱(DPPC)和二肉豆蔻酰磷脂酰胆碱(DMPC)为载体,制备了NGR肽(Asn-Gly-Arg)修饰的主动靶向脂质体,并用其负载香豆素-6.结果表明,4种脂质体的粒径为120～160 nm,粒度分布均匀,ζ电位接近中性,包封率均在95％以上.差示扫描量热分析(DSC)表明,4种脂质体的相变温度(Tm)值由高至低分别为DSPC脂质体＞HSPC脂质体＞DPPC脂质体＞DMPC脂质体.以CD13高表达的HT1080细胞为模型,采用流式细胞仪、激光共聚焦显微镜观察评价脂质体的入胞效果.结果显示,脂质体的入胞效率与Tm值呈正相关.     

颐康冲剂对喃氟啶抗肿瘤作用及其毒性影响的实验研究

颐康冲剂由虫草、当归、红参等16味药材提制而成。实验结果表明，不同剂量的颐康冲剂与喃氟啶伍用均能明显提高喃氟啶对小鼠移植肿瘤S180．Lewis及H22的抑瘤率，与单用喃氟啶相比。p＜0．05～0．01。对喃氟啶所致小鼠白细胞减少，免疫器官萎缩、巨噬细胞吞噬功能降低及脾脏中NK细胞活性下降等毒副反应均有明显保护作用。     

抗癌药双喃氟啶的合成

双喃氟啶(FD-1)是一个新的抗代谢类抗肿瘤药物,它与抗癌药喃氟啶(FT-207)同属于5-氟尿嘧啶(5-Fu)的衍生物。化学名:1,3-双(四氢呋喃基)-5-氟尿嘧啶。经动物实验结果表明:口服双喃氟啶后在血和组织中的5-Fu浓度比口服喃氟啶后的5-Fu浓度高5～7倍;尤其在肿瘤组织中的5-Fu浓度前者比后者要高8～12倍。双喃氟啶的毒性仅为喃氟啶的1/3左右。又经生化研究阐明,双喃氟啶系通过二条途径代谢为5-Fu,一条途径先代谢为喃氟啶;另一条途径先代谢为3-FT,它的抑瘤率较FT-207和FD-1都高,因而双喃氟啶对胃     

正相高效液相色谱法测定家兔血浆中喃氟啶含量

本文报道用正相高效液相色谱法测定家兔血浆中喃氟啶的含量。血浆样品的氯仿提取液进入5-10μm的YWG硅胶色谱柱,用氯仿乙酸乙酯(1:1)洗脱、UV254nm检测,呋喃丙胺为内标。本法检测限量为20ng,在测定浓度范围内线性良好。曾用此法测定并初步计算了家兔口服喃氟啶后的血浆浓度及主要动力学参数。     

左旋咪唑对喃氟啶抑瘤活性的增强作用及其毒性影响的实验研究

本文研究了左旋咪唑对喃氟啶抑瘤活性的增强作用及其毒性影响。实验结果表明,不同剂量的左旋咪唑与喃氟啶伍用均能明显提高喃氟啶对小鼠移植肿瘤s_(180)、Lewis及H_(22)的抑瘤率。与单用喃氟啶相比,P值<0.05—0.01,其中低剂量的左旋咪唑(?)mg/kg)抑瘤效果较佳。对喃氟啶所致小鼠白细胞减少、免疫器官萎缩、巨噬细胞吞噬功能降低及NK细胞活性下降等均有显著保护作用。     

Reconsideration of drug release from temperature-sensitive liposomes

The liposomal phase transition temperature was monitored in unstirred suspensions using a differential scanning calorimeter. The main and pre-transition temperatures under conditions of stirring were measured by the change in 90 degrees light scattering using a fluorescence spectrophotometer. Both methods show the same main transition temperature either with or without stirring. Temperature sensitive liposomes were made of DPPC (dipalmitoylphosphatidylcholine), DMPC (dimylisitoylphosphatidylcholine) or DSPC (distearoylphosphatidylcholine). The calcein release profile from the liposomes depends on the stirring time of the liposome suspension at the main transition temperature. For 1 h incubation, the leakage profile with and without stirring is similar. It had been hypothesized that temperature sensitive liposomes released drug at the main-transition temperature. However, calcein leakage from liposomes is observed also at the pre-transition temperature. Thus, a liposomal encapsulated drug will likely leak from DPPC liposomes at body temperature (37 degrees C), even if the liposomes were designed to have a higher main transition temperature.     

Radioprotective effect of transferrin targeted citicoline liposomes

The high level of expression of transferrin receptors (Tf-R) on the surface of endothelial cells of the blood-brain-barrier (BBB) had been widely utilized to deliver drugs to the brain. The primary aim of this study was to use transferrin receptor mediated endocytosis as a pathway for the rational development of holo-transferrin coupled liposomes for drug targeting to the brain. Citicoline is a neuroprotective agent used clinically to treat for instance Parkinson disease, stroke, Alzheimer's disease and brain ischemia. Citicoline does not readily cross the BBB because of its strong polar nature. Hence, citicoline was used as a model drug. (Citicoline liposomes have been prepared using dipalmitoylphosphatidylcholine (DPPC) or distearoylphosphatidylcholine (DSPC) by dry lipid film hydration-extrusion method). The effect of the use of liposomes composed of DPPC or DSPC on their citicoline encapsulation efficiency and their stability in vitro were studied. Transferrin was coupled to liposomes by a technique which involves the prevention of scavenging diferric iron atoms of transferrin. The coupling efficiency of transferrin to the liposomes was studied. In vitro evaluation of transferrin-coupled liposomes was performed for their radioprotective effect in radiation treated cell cultures. In this study, OVCAR-3 cells were used as a model cell type over-expressing the Tf-R and human umbilical vein endothelial cells (HUVEC) as BBB endothelial cell model. The average diameter of DPPC and DSPC liposomes were 138 +/- 6.3 and 79.0 +/- 3.2 nm, respectively. The citicoline encapsulation capacity of DPPC and DSPC liposomes was 81.8 +/- 12.8 and 54.9 +/- 0.04 microg/micromol of phospholipid, respectively. Liposomes prepared from DSPC showed relatively better stability than DPPC liposomes at 37 degrees C and in the presence of serum. Hence, DSPC liposomes were used for transferrin coupling and an average of 46-55 molecules of transferrin were present per liposome. Free citicoline has shown radioprotective effect at higher doses tested. Interestingly, encapsulation of citicoline in pegylated liposomes significantly improved the radioprotective effect by 4-fold compared to free citicoline in OVCAR-3 but not in HUVEC. Further, citicoline encapsulation in transferrin-coupled liposomes has significantly improved the radioprotective effect by approximately 8-fold in OVCAR-3 and 2-fold in HUVEC cells with respect to the free drug. This is likely due to the entry of citicoline into cells via transferrin receptor mediated endocytosis. In conclusion, our results suggest that low concentrations of citicoline encapsulated in transferrin-coupled liposomes could offer therapeutic benefit in treating stroke compared to free citicoline.     

The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations

Liposomes are colloidal carriers that form when certain (phospho)lipid molecules are hydrated in an aqueous media with some energy input. The ideal liposome formulation with optimum stability will improve drug delivery by decreasing the required dose and increasing the efficacy of the entrapped drug at the target organ or tissue. The most important parameter of interest in this article was to compare the efficacy of three different liposomes formulated with DSPC, DMPC, and DPPC, all saturated neutral phospholipids with different acyl chain lengths and transition temperatures. DMPC has a phase transition temperature (Tc) below 37°C, whereas the other two phospholipids possess Tcs above the physiological temperature. These lipids were then added to a cholesterol concentration of 21% to optimize the stability of the vesicles. The liposomes were prepared by a sonication and incubated in phosphate buffered saline (PBS) at 4°C and 37°C. The encapsulation efficiency, initial size, and drug retention of the vesicles were tested over a 48-hr period employing radiolabeled inulin as a model drug. The phase transition temperature of liposomes, which depends on the Tc of the constituent lipids, was an important factor in liposome stability. Of all the liposomes tested, the greatest encapsulation efficiency was found for the DSPC liposomes (2.95%) that also had the greatest drug retention over 48 hr at both 4°C (87.1 ± 6.8%) and 37°C (85.2 ± 10.1%), none of these values being significantly different from time zero. The lowest drug retention was found for DMPC liposomes for which a significant difference in drug retention was seen after only 15 min at both 4°C (47.3 ± 6.9%) and 37°C (53.8 ± 4.3%). The DPPC liposomes showed a significant difference in drug retention after 3 hr at 4°C (62.1 ± 8.2%) and after 24 hr at 37°C (60.8 ± 8.9%). Following the initial drop at certain time intervals a plateau was reached for all of the liposome formulations after which no significant difference in drug retention was observed. In conclusion, liposomes with higher transition temperatures appear to be more stable in PBS either at 4°C or 37°C, indicating that the increase in acyl chain length (and therefore transition temperature) is directly proportional to stability.     

The Effect of Different Lipid Components on the In Vitro Stability and Release Kinetics of Liposome Formulations

Liposomes are colloidal carriers that form when certain (phospho)lipid molecules are hydrated in an aqueous media with some energy input. The ideal liposome formulation with optimum stability will improve drug delivery by decreasing the required dose and increasing the efficacy of the entrapped drug at the target organ or tissue. The most important parameter of interest in this article was to compare the efficacy of three different liposomes formulated with DSPC, DMPC, and DPPC, all saturated neutral phospholipids with different acyl chain lengths and transition temperatures. DMPC has a phase transition temperature (Tc) below 37°C, whereas the other two phospholipids possess Tcs above the physiological temperature. These lipids were then added to a cholesterol concentration of 21% to optimize the stability of the vesicles. The liposomes were prepared by a sonication and incubated in phosphate buffered saline (PBS) at 4°C and 37°C. The encapsulation efficiency, initial size, and drug retention of the vesicles were tested over a 48-hr period employing radiolabeled inulin as a model drug. The phase transition temperature of liposomes, which depends on the Tc of the constituent lipids, was an important factor in liposome stability. Of all the liposomes tested, the greatest encapsulation efficiency was found for the DSPC liposomes (2.95%) that also had the greatest drug retention over 48 hr at both 4°C (87.1 ± 6.8%) and 37°C (85.2 ± 10.1%), none of these values being significantly different from time zero. The lowest drug retention was found for DMPC liposomes for which a significant difference in drug retention was seen after only 15 min at both 4°C (47.3 ± 6.9%) and 37°C (53.8 ± 4.3%). The DPPC liposomes showed a significant difference in drug retention after 3 hr at 4°C (62.1 ± 8.2%) and after 24 hr at 37°C (60.8 ± 8.9%). Following the initial drop at certain time intervals a plateau was reached for all of the liposome formulations after which no significant difference in drug retention was observed. In conclusion, liposomes with higher transition temperatures appear to be more stable in PBS either at 4°C or 37°C, indicating that the increase in acyl chain length (and therefore transition temperature) is directly proportional to stability.     

Radioprotective effect of transferrin targeted citicoline liposomes

The high level of expression of transferrin receptors (Tf-R) on the surface of endothelial cells of the blood–brain-barrier (BBB) had been widely utilized to deliver drugs to the brain. The primary aim of this study was to use transferrin receptor mediated endocytosis as a pathway for the rational development of holo-transferrin coupled liposomes for drug targeting to the brain. Citicoline is a neuroprotective agent used clinically to treat for instance Parkinson disease, stroke, Alzheimer's disease and brain ischemia. Citicoline does not readily cross the BBB because of its strong polar nature. Hence, citicoline was used as a model drug. (Citicoline liposomes have been prepared using dipalmitoylphosphatidylcholine (DPPC) or distearoylphosphatidylcholine (DSPC) by dry lipid film hydration–extrusion method). The effect of the use of liposomes composed of DPPC or DSPC on their citicoline encapsulation efficiency and their stability in vitro were studied. Transferrin was coupled to liposomes by a technique which involves the prevention of scavenging diferric iron atoms of transferrin. The coupling efficiency of transferrin to the liposomes was studied. In vitro evaluation of transferrin-coupled liposomes was performed for their radioprotective effect in radiation treated cell cultures. In this study, OVCAR-3 cells were used as a model cell type over-expressing the Tf-R and human umbilical vein endothelial cells (HUVEC) as BBB endothelial cell model. The average diameter of DPPC and DSPC liposomes were 138 ± 6.3 and 79.0 ± 3.2 nm, respectively. The citicoline encapsulation capacity of DPPC and DSPC liposomes was 81.8 ± 12.8 and 54.9 ± 0.04 μg/μmol of phospholipid, respectively. Liposomes prepared from DSPC showed relatively better stability than DPPC liposomes at 37°C and in the presence of serum. Hence, DSPC liposomes were used for transferrin coupling and an average of 46–55 molecules of transferrin were present per liposome. Free citicoline has shown radioprotective effect at higher doses tested. Interestingly, encapsulation of citicoline in pegylated liposomes significantly improved the radioprotective effect by 4-fold compared to free citicoline in OVCAR-3 but not in HUVEC. Further, citicoline encapsulation in transferrin-coupled liposomes has significantly improved the radioprotective effect by approximately 8-fold in OVCAR-3 and 2-fold in HUVEC cells with respect to the free drug. This is likely due to the entry of citicoline into cells via transferrin receptor mediated endocytosis. In conclusion, our results suggest that low concentrations of citicoline encapsulated in transferrin-coupled liposomes could offer therapeutic benefit in treating stroke compared to free citicoline.     

Stability of SUV liposomes in the presence of cholate salts and pancreatic lipases: effect of lipid composition.

The effect of bile salts (sodium cholate and sodium taurocholate), and pancreatic lipases on the structural integrity of SUV liposomes of different lipid compositions was studied. Liposomal membrane integrity was judged by bile salt or pancreatin-induced release of vesicle encapsulated 5,6-carboxyfluorescein, and vesicle size distribution before and after incubations. Bile salt concentration was 10 mM, while a saturated solution of pancreatin (mixed with equal volume of liposomes) was utilized. Results agree with earlier studies, demonstrating the instability of liposomes composed of lipids with low transition temperatures (PC and DMPC) in presence of cholates. Addition of cholesterol (1:1 lipid:chol molar ratio) does not substantially increase the encapsulated molecule retention. Nevertheless, liposomes composed of lipids with high transition temperatures (DPPC, DSPC and SM), retain significantly higher amounts of encapsulated material, under all conditions studied. Furthermore, the vesicles formed by mixing cholesterol with these lipids will possibly be sufficiently stable in the gastrointestinal tract for long periods of time. Sizing results reveal that in most cases release of encapsulated molecules is mainly caused by their leakage through holes formed on the lipid bilayer. However, in stearylamine containing DPPC and DSPC vesicles, the cholate-induced drastic decrease in vesicle size suggests total liposome disruption as the possible mechanism of encapsulated material immediate release.     

Solubilisation of dipalmitoylphosphatidylcholine bilayers by sodium taurocholate: A model to study the stability of liposomes in the gastrointestinal tract and their mechanism of interaction with a model bile salt

In order to better understand the mechanism of destabilization of liposomes used as drug carriers for oral administration by bile salts, the insertion and partition of sodium taurocholate (TC) into small unilamellar vesicles (SUV) and multilayers (ML) of dipalmitoylphosphatidylcholine (DPPC) were examined by continuous turbidity analysis and DSC. Optical density was recorded during the progressive solubilisation of DPPC SUV and ML into DPPC/TC mixed micelles by varying the rate of TC addition and the temperature. The results show that the insertion and diffusion of TC in the DPPC membrane is a slow process influenced by the polymorphism of the lipid, independently of its organisation. This dynamic study mimics physiological phenomena of the digestion of liposomes. In the gastrointestinal tract, DPPC SUV would be more resistant to TC than egg phosphatidylcholine (EPC) SUV [K. Andrieux, L. Forte, S. Lesieur, M. Paternostre, M. Ollivon, C. Grabielle-Madelmont, Insertion and partition of sodium taurocholate into egg phosphatidylcholine vesicles, Pharm. Res. 21 (2004) 1505-1516] because of the lower insertion of TC into DPPC bilayer at 37 °C at low TC concentration in the medium (fasted conditions). At high TC concentration (postprandially or after lipid absorption), the use of DPPC to prepare liposomes will delay or reduce the liberation of a drug encapsulated into liposomes in the gastrointestinal tract. As a conclusion, the addition of DPPC appears an attractive strategy to formulate orally administered liposomes.     

Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment

The primary goal of this study was the production of liposomes encapsulating kanamycin for drug administration by inhalation. The selected drug is indicated for multiresistant tuberculosis, and administration through inhalation allows both local delivery of the drug to the lungs and systemic therapy. The ethanol injection method used for the liposome production is easily scaled up and is characterized by simplicity and low cost. Vesicles were prepared using different lipid compositions, including hydrogenated soybean phosphatidylcholine and cholesterol (SPC/Chol), egg phosphatidylcholine and cholesterol (EPC/Chol), distearoyl phosphatidylcholine and cholesterol (DSPC/Chol), distearoyl phosphatidylcholine, dimyristoyl phosphatidylethanolamine and cholesterol (DSPC/DMPE/Chol), dipalmitoyl phosphatidylcholine and cholesterol (DPPC/Chol) and dipalmitoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol and cholesterol (DPPC/DPPG/Chol). The effects of different operational conditions for vesicle production and drug encapsulation were evaluated, aiming at a compromise between final process cost and suitable vesicle characteristics. The best performance concerning drug incorporation was achieved with the DSPC/Chol system, although its production cost was considerably larger than that of the natural lipids formulations. Encapsulation efficiencies up to 63% and final drug to lipid molar ratios up to 0.1 were obtained for SPC/Chol vesicles presenting mean diameters of 132 nm incubated at 60 degrees C with the drug for 60 min at an initial drug-to-lipid molar ratio of 0.16.     

Transdermal lontophoretic delivery of colchicine encapsulated in liposomes

Iontophoresis is useful for the transdermal delivery of charged drugs. However, nonionized drugs either have a low flux (due to electro-osmosis) or cannot be delivered using this technique. Because ionized or nonionized drugs can be encapsulated in charged liposomes, it was hypothesized that charged liposomes can deliver neutral or nonionized drug efficiently by iontophoresis. Colchicine, a neutral drug, was encapsulated in large unilamellar vesicles (LUVs), prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) along with cholesterol (1:0.5 mole ratio). Multilamellar vesicles (MLVs) were prepared by the thin-film hydration method and LUVs were obtained by extruding MLVs through polycarbonate filters of 200 nm pore size. Positive charge was induced in the liposomes by adding stearylamine and negative charge by adding dicetyl phosphate. Nonencapsulated drug was separated from LUVs by the Ficoll density gradient method. Positively charged LUVs were delivered under the anode, negatively charged LUVs under the cathode, and neutral LUVs without current using Franz cells and human cadaver skin. Plain colchicine as well as colchicine encapsulated in positively charged LUVs was delivered better under the anode compared with the cathode and passive conditions. Delivery of colchicine encapsulated in positively charged DSPC liposomes was four to five times greater than that of plain colchicine and two to three times greater than that of colchicine encapsulated in DMPC or DPPC liposomes. Because LUVs prepared with DMPC and DPPC were fluid at 37°C, the encapsulated drug leaked during iontophoresis and therefore the delivery was less. Delivery of colchicine was lower under the cathode due to the change in pH during iontophoresis, which, as observed in high-performance liquid chromatographic analysis, caused degradation of the drug. Thus, it can be concluded that iontophoresis of colchicine encapsulated in positively charged DSPC liposomes can improve its delivery across human cadaver skin     

Partition of Dopamine Antagonists into Synthetic Lipid Bilayers: the Effect of Membrane Structure and Composition

Abstract— Partition coefficients, K_p, of four dopamine antagonists (pimozide, fluspirilene, haloperidol and domperidone) between the aqueous phase and lipid bilayer vesicles were determined as a function of lipid chain length, unsaturation and temperature encompassing the range of the lipid phase transition. Model membranes of egg phosphatidylcholine (PC), dimyristoyl (DMPC)-, dipalmitoyl (DPPC)-, distearoyl (DSPC)- and dioleoyl (DOPC)-phosphatidylcholines were studied. K_p values of the drugs are different in the various membranes under study and depend on temperature, aliphatic carbon chain-length and on the presence of unsaturation in the aliphatic lipid chain. First-order transition of membrane lipids from the gel to the liquid crystalline state is accompanied by a sharp increase of the partition coefficient of pimozide and fluspirilene in DMPC, DPPC and DSPC bilayers. For domperidone, K_p values are maximal within the midpoint of phase transition of DMPC and DPPC, while for DSPC K_p values increase progressively with increasing temperature. Haloperidol K_p values display a maximum at the mid-point of phase transition of DMPC, while a progressive increase of K_p is observed in DPPC and DSPC. The four drugs are easily accommodated in bilayers of short aliphatic chain lipids (DMPC), the partition coefficients being 17137 for pimozide, 18 700 for fluspirilene, 686 for domperidone and 722 for haloperidol, at temperatures 10°C below the mid-point of the lipid phase transition. Except for haloperidol, the partition of the drugs in DOPC (18:1) is higher than that in DSPC (18:0) bilayers at a temperature above the phase transition temperature of both lipids. From our experiments we can conclude that artificial membranes are useful models to understand the physicochemical mechanisms involved in the interaction of dopamine antagonists with biological membranes.