ISSN:1061-186X    

DOI:10.3109/10611869408996808

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractAnimal immunization studies by numerous laboratories have shown that liposomes promote humoural and cell-mediated immunity to a wide spectrum of bacterial, protozoan and viral antigens as well as tumour cell antigens, venoms and allergens. Adjuvanticity depends on liposomal structural characteristics which determine vesicle fate in vivo and, thus, the mode of antigen interaction with antigen-presenting cells. Adjuvanticity is further promoted by receptor mediated targeting of liposomes to macrophages, or the presence of other adjuvants including cytokines. The immunoadjuvant function of liposomes is supplemented by their ability to act as a carrier for co-entrapped B and T-cell epitopes, thus eliminating the need for a carrier protein. Recently, a technique has been developed for the entrapment of live or attenuated microbial vaccines into giant liposomes under conditions which retain their viability. Liposomes containing microbial vaccines (together with other soluble antigens or cytokines) could be used as carriers of vaccines in cases where there is a need to prevent interaction of vaccines with maternal antibodies or preformed antibodies to vaccine impurities.

ISSN:1061-186X    

DOI:10.3109/10611869408996809

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractTo study the role of macrophages in immune and non-immune defence mechanisms, a new technique to eliminate macrophages has been developed. This technique uses the capability of macrophages to ingest and digest particulate compounds. As particulate compound liposomes with entrapped clodronate are used. Macrophages will ingest these liposomes and after fusion of their endosomes with their lysosomes the bilayers are disrupted under influence of phospholipases and the clodronate is released into the cytoplasm. If the intracellular concentration of free clodronate reaches sufficiently high values, the macrophage will die. The applications of the approach and some of the results obtained up to now using this macrophage 'suicide' technique are discussed.

ISSN:1061-186X    

DOI:10.3109/10611869408996810

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThe use of liposomes in the treatment of severe infections is under investigation. Classical liposomes which localize in cells of the mononuclear phagocyte system (MPS) can be exploited in two ways. First for targeting of macrophage modulators such as muramyl peptides or IFN-γ, to stimulate the cells of the MPS to maximal blood clearance capacity. This enhanced nonspecific anti-infectious resistance is important as in immunocompromised patients micro-organisms frequently appear in the blood from a local infection. Secondly, classical liposomes are successfully used as carriers of antibiotics in experimental intracellular parasitic-, viral-, fungal- or bacterial infections in MPS tissues. Based on these data extensive studies in patients with severe fungal infections have demonstrated successful treatment with liposomal or lipid-complexed amphotericin B. More recently, liposomal amphotericin B appeared to be effective in patients with drug-resistant visceral leishmaniasis. For the treatment ofMycobacterium aviumcomplex infection in AIDS patients the efficacy of liposomal gentamicin is under investigation. With respect to infections in non-MPS tissues the applicability of Stealth®liposomes characterized by long circulation half-lives is under investigation. Substantial localization of these liposomes in infected lung tissue of rats was demonstrated. Preliminary data in experimental bacterial lung infection showed superior efficacy of antibiotic encapsulated in Stealth®liposomes.

ISSN:1061-186X    

DOI:10.3109/10611869408996811

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractPreviously, we have shown that liposomal amphotericin B (L-AmpB) is less nephrotoxic than and equally as effective as free AmpB as treatment of patients with systemic fungal infections; The mechanism of L-AmpB's enhanced therapeutic index, however, remains unknown. This review discusses AmpB's association with lipoproteins, predominantly high-density lipoproteins (HDL) and the biological relevance of transferring AmpB to HDL. We observed that AmpB was less toxic to pig kidney cells when associated with HDL but still remains toxic when associated with low-density lipoproteins (LDL). AmpB's association with HDL or LDL does not alter its antifungal activity. We further found that these kidney cells express high- and low-affinity LDL receptors but only low-affinity HDL receptors. The reduced renal cytotoxicity of HDL-associated AmpB may be due to its lack of interaction with the renal cells, since they have no HDL receptors. Since AmpB interacts with cholesteryl esters in serum, whose transfer between HDL and LDL is regulated by lipid transfer protein (LTP), we addressed the role of this protein on the distribution of AmpB between HDL and LDL. The addition of LTP altered the lipoprotein distribution of AmpB but not of L-AmpB. Furthermore L-AmpB, but not AmpB (except at 20μg/ml), inhibited the LTP-mediated transfer of cholesterol esters from HDL to LDL. It appears therefore, that the decreased nephrotoxicity associated with L-AmpB administration is related to its predominant distribution to HDL, which is regulated by inhibiting of LTP-mediated cholesterol esters transfer activity.

ISSN:1061-186X    

DOI:10.3109/10611869408996812

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractPhospholipid (dipalmitoylphosphatidylcholine (DPPC) plus phosphatidylinositol (PI)) proteoliposomes with surface bound lectins (succinylated concanavalin A (s con A) and wheat germ agglutinin (WGA)) have been prepared covering a range of size and surface density of lectin. Negatively charged phospholipid liposomes from DPPC-PI mixtures covering a range of PI mole % and positively charged liposomes from DPPC-cholesterol-stearylamine (SA) mixtures covering a range of SA mole % have been prepared. The targeting of the liposomes and proteoliposomes to a range of oral and skin-associated bacterial biofilms has been investigated. The oral bacteria Streptococcusmutansandgordoniiand the skin-associated bacteriumCoryneform hofmannican be targeted with s con A bearing proteoliposomes while the skin associated bacteriumStaphylococcus epidermidiscan be targeted with WGA bearing proteoliposomes. Both oral and skin-associated bacteria can be targeted with positively charged liposomes although the extents of adsorption to the biofilm are low except forStaphylococcus epidermidis. In the case of negatively charged liposomes targeting is critically dependent on the PI content of the liposomes and for all the bacteria studied optimum levels PI for targeting have been found. The adsorption of the oral bacteriumStreptococcus gordoniito immobilised monolayers having the optimum PI level for adsorption has been studied by total internal reflection microscopy (TIRM). Both the phospholipid and proteoliposomes have been used to deliver the bactericide Triclosan®to biofilms. All the systems studied inhibited bacterial growth to varying degrees. The proteoliposomes and the DPPC-PI liposomes containing low levels of Triclosan®inhibited bacterial growth more effectively than the equivalent levels of free bactericide.

ISSN:1061-186X    

DOI:10.3109/10611869408996813

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractTargeted delivery of macrophage activating agents is an attractive approach to treat micrometastatic disease. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a potent activator of monocytes/macrophages in humans, mice, and dogs. We have conducted clinical trials in dogs with malignant and highly metastatic spontaneous tumors. Presented are results of our trials evaluating L-MTP-PE in combination with surgery and chemotherapy in dogs with spontaneous osteosarcoma and hemangiosarcoma, particularly relevant malignancies having many similarities to human cancer. Osteosarcoma dogs received chemotherapy following surgery (cisplatin q 28 days×4). At completion of chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p<0.021). Dogs with splenic hemangiosarcoma received combination chemotherapy following surgery (doxorubicin and cyclophosphamide q 21 days×4). At the first chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p<0.03). These studies show that L-MTP-PE is an effective agent for treatment of metastasis and can be safely administered in combination with chemotherapy.

ISSN:1061-186X    

DOI:10.3109/10611869408996814

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractAdvanced liposomal therapeutics has been attained by liposome surface modification, initially with specific glycolipids and subsequently with surface-grafted PEG, reducingin vivorapid recognition and uptake, giving prolonged blood circulation, and providing selective localization in tumors and other pathological sites, as described in recent reviews. The result is improved efficacy of encapsulated agents. The surface PEG may produce a steric barrier, as described for colloids. Reducedin vivouptake may result from inhibition of plasma-protein adsorption, or opsonization, by the steric coating. Several physical studies support this mechanism, including electrophoretic mobility (zeta potential). Our previous results for 2000-dalton PEG indicated a coating thickness about 5 nm, in agreement with independent measurements. We report here results for 750 to 5000-dalton PEGs. The calculated coating thickness increases with molecular weight in a nonlinear fashion. The dependence of blood circulation and tissue distribution on PEG molecular weight correlates with zeta-potential estimates of PEG-coating thickness. Effects on tissue distribution are reported for liver and spleen, the major phagocytic organs. The biological properties of these liposomes depend on the surface polymer rather than the lipid bilayer, yielding important advantages for lipid-mediated control of drug interaction and release without affecting the biodistribution.

ISSN:1061-186X    

DOI:10.3109/10611869408996815

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractThis review will highlight work done in our laboratories evaluating topical liposomal delivery in a wide variety of animal models and human skin using bothin vivoandin vitrotechniques. The mechanism by which liposomes facilitate deposition of drugs into the skin and some potential applications of topically applied liposomes will be discussed. Particular emphasis will be placed on the development of analytical techniques that allow the quantification of drug levels in the various skin strata and in pilosebaceous structures. Appropriate models of skin representing the two cases, as well as those wherein both routes are available for skin deposition, were examined using a wide variety of liposomal preparations containing radiolabeled and fluorescent molecules as marker compounds.

ISSN:1061-186X    

DOI:10.3109/10611869408996816

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

AbstractVitamin D3-derivatives are known to be effective in differentiation and proliferation of epidermal cells. However, under certain circumstances, they also may show a hypercalcamic activity which can be a serious limitation in their use for dermatological application. For keeping small the negative side effects of vitamin D3-derivatives and for increasing the drug concentration in the skin we investigated their incorporation in liposomes to optimize their use forpsoriasistreatment.The incorporation of vitamin D3-derivatives in liposomes of different lipid composition was studied by HPLC, DSC and freeze-fracture electron microscopy. Incorporation rates of more than 80% of the offered drug were found with significant variations related to the number of hydroxyl-groups in the A-ring, opened or closed B-ring, and some modifications in the side chain of the steroid-molecules. In general, the incorporation rates in egg-PC liposomes have been of about 3% up to 10% higher than in DMPC liposomes. Results, obtained by DSC and freeze-fracture electron microscopy, show a depression of the phase transition of DMPC bilayers by incorporation of vitamin D3already at a concentration of 10 mol%. These results support the idea that vitamin D3and its analoga investigated are incorporated into the lipid bilayer modifying there the lipid-lipid interactions.

ISSN:1061-186X    

DOI:10.3109/10611869408996817

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor