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51.
Abstract Propranolol (1-isopropylamino-3-(1-naphtoloxy)-propan-2-ol) a β-adren-ergic receptor blocking agent was found to cause changes of transmembraneous pH in liposomes prepared from Soy-lecithin and cardiolipin. When the external pH was neutral and the internum of the liposomes acidic, the drug decreased the pH gradient. When the externum was acidic and the internum neutral, the gradient was increased by the drug. The effect of butacaine was similar to that of propranolol, while procaine, timolol and practolol were ineffective. It is suggested that the charged form of propranolol is bound to the membrane and dislocates protons from binding sites in the membrane and that the uncharged form of propranolol penetrates the membrane. After penetration it could associate with protons in the intraliposomal compartment and hence increase the pH of the interior. Depending on the direction of the pre-existing proton gradient propranolol would thus be able to increase or decrease the pH difference across the liposomal membrane. 相似文献
52.
Arpicco S Canevari S Ceruti M Galmozzi E Rocco F Cattel L 《Il Farmaco; edizione pratica》2004,59(11):869-878
We synthesized new cationic lipids, analogue to N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) and 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethylammonium bromide (DMRIE), in order to compare those containing a dodecyl chain with those having a relatively long chain with two or five double bonds, such as squalenyl and dihydrofarnesyl derivatives, or complex saturated structures, such as squalane derivatives. The fusogenic helper lipid dioleoylphosphatidylethanolamine (DOPE) was added to cationic lipids to form a stable complex. Liposomes composed of 50:50 w/w cationic lipid/DOPE were prepared and incubated with plasmidic DNA at various charge ratios and the diameter and zeta potential of the complexes were measured. The surface charge of the DNA/lipid complexes can be controlled by adjusting the cationic lipid/DNA ratio. Finally, we tested the in vitro transfection efficiency of the cationic lipid/DNA complexes using different cell lines. The transfection efficiency was highest for the dodecyloxy derivative containing a single hydroxyethyl group in the head, followed by the dodecyloxy and the farnesyloxy trimethylammonium derivatives. Instead the C27 squalenyl and C27 squalanyl derivatives resulted inactive. 相似文献
53.
Incorporation of antibiotics in liposomes designed for tuberculosis therapy by inhalation 总被引:2,自引:0,他引:2
Liposomal encapsulation of tuberculostatic drugs can potentially increase their therapeutic index. The incorporation of isoniazid, pyrazinamide, rifampicin, ethionamide, and streptomycin in extruded distearoylphosphatidylcholine/cholesterol liposomes designed for administration through inhalation was evaluated. Ethionamide and rifampicin were incorporated during lipid film formation, whereas solutions of the remaining drugs were used to hydrate preformed lipid bilayers. Final drug to lipid ratios around 0.3 were achieved for isoniazid and pyrazinamide, and mean vesicle diameters varied from 286 to 329 nm. No expressive drug leakage or mean vesicle diameter changes occurred during 3 weeks. No significant incorporation was achieved for streptomycin, ethionamide, and rifampicin. 相似文献
54.
Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy 总被引:10,自引:0,他引:10
Gabizon AA 《Cancer investigation》2001,19(4):424-436
Pegylated liposomal doxorubicin (Doxil, Caelyx) is a formulation of doxorubicin in poly(ethylene glycol)-coated (stealth) liposomes with a prolonged circulation time and unique toxicity profile. We review the preclinical and clinical pharmacology as well as recent clinical data obtained in specific cancer types. Doxil liposomes retain the drug payload during circulation and accumulate preferentially in tissues with increased microvascular permeability, as often is the case of tumors. Doxil toxicity profile is drastically different from that of doxorubicin, and is characterized by dominant and dose-limiting mucocutaneous toxicities, mild myelosupression, minimal alopecia, and no apparent cardiac toxicity. Although the single maximum tolerated dose (MTD) of Doxil is actually lower than that of conventionally administered doxorubicin, the cumulative MTD dose of Doxil may be substantially greater than that of free doxorubicin. Doxil is probably one of the most active agents in AIDS-related Kaposi's sarcoma and has a definite role in management of recurrent ovarian cancer. The potential of Doxil in the treatment of other cancer types and the opportunities it offers in combination with other drugs and therapeutic modalities are under active investigation. 相似文献
55.
The objective of this study is to determine the effect of various neutral liposomes on corneal and conjunctival permeability of didanosine (ddI), an antiviral drug. Multi-lamellar vesicles (MLVs), large unilamellar vesicles (LUVs), and sonicated multi-lamellar vesicles (SMLVs) encapsulating ddI (with trace quantities of 3HddI) were prepared using distearoyl phosphatidylcholine (DSPC), a neutral lipid. The liposomes contained 14C-cholesteryl oleate as a lipid tracer. Liposome formulations containing free and encapsulated drug (f + e) and those containing only encapsulated drug (e) of an equal quantity were compared with free drug in this study. The permeability studies were conducted in the mucosal to serosal direction across excised rabbit cornea and conjunctiva. The percent encapsulation of ddI in MLVs, LUVs, and SMLVs was 25.66 0.30, 26.56 0.57, and 19.41 0.30, respectively. The mean particle size of MLVs, LUVs, and SMLVs containingfree and encapsulated drug was 3058, 774, and 270 nm, respectively. With all liposome formulations tested, the percent uptake of lipid by tissues was higher compared to ddI uptake. While ddI permeated across the tissues, the lipid tracer did not permeate in detectable quantities.The SMLV(e) formulation was better than the SMLV(f + e) formulation with respect to initial flux and tissue uptake in both tissues and permeability across conjunctiva. In general, the permeability coefficient, initial flux, and tissue levels of ddI at the end of the transport study were lower in the presence of all liposome formulations compared to free drug. Thus, neutral liposomal encapsulation is not a suitable approach to enhance the corneal or conjunctival transport or uptake of ddI. 相似文献
56.
Petrikovics I McGuinn WD Sylvester D Yuzapavik P Jiang J Way JL Papahadjopoulos D Hong K Yin R Cheng TC DeFrank JJ 《Drug delivery》2000,7(2):83-89
This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine. 相似文献
57.
David A. Christian 《European journal of pharmaceutics and biopharmaceutics》2009,71(3):463-474
Polymersomes are polymer-based vesicular shells that form upon hydration of amphiphilic block copolymers. These high molecular weight amphiphiles impart physicochemical properties that allow polymersomes to stably encapsulate or integrate a broad range of active molecules. This robustness together with recently described mechanisms for controlled breakdown of degradable polymersomes as well as escape from endolysosomes suggests that polymersomes might be usefully viewed as having structure/property/function relationships somewhere between lipid vesicles and viral capsids. Here we summarize the assembly and development of controlled release polymersomes to encapsulate therapeutics ranging from small molecule anti-cancer drugs to siRNA and therapeutic proteins. 相似文献
58.
59.
Pilar Sánchez Henarejos Silverio Ros Martínez Gema R. Marín Zafra José L. Alonso Romero Agustín Navarrete Montoya 《Clinical & translational oncology》2009,11(7):486-487
Pegylated liposomal doxorubicin (PLD) is a drug whose use is increasingly common. It has been associated with a lower rate
of haematologic and cardiac side effects than its nonencapsulated form. However, mucocutaneous toxicity is quite frequent
and can be severe. Here we provide a case report of a patient who developed an intertrigolike eruption during treatment with
PLD. 相似文献
60.
设计了十一种冻干制剂的配方,通过外观检查和稳定性考查,从中筛选出最佳配方,即以乳糖为赋形剂且冻干前浓度为2.5%的制剂。探讨了各种条件对制备SOD脂质体的影响,选出了提高包嵌率的较好条件。改进了测定SOD活性的极谱法,测定了SOD水溶液和两种SOD脂质体在兔血内SOD活性的变化,初步证实所制得的脂质体可延长SOD在体内的停留时间。 相似文献