Liposomes parasites

Liposomal AMB has been shown to be effective in experimental fungal and also parasitic diseases (reviewed by Emmen and Storm,... 

Peeters, P. A. M., Brunink, B. G., Eling, W. M. C., and Crommelin, D. J. A. (1989). Therapeutic effect of chloroquirie (CQ) containing immunoliposomes in rats infected with Plasmodium berghei parasitized mouse red blood cells comparison with combinations of antibodies and CQ or liposomal CQ, Biochim. Biophys Acta, 981, 269-276. 

In one experiment, LC-AmB was compared with AmBisome (small unilamellar liposomes). LC-AmB was found to have an ED50 of 0.19 mg/kg and an ED90 of 0.51 mg/kg, whereas for AmBisome both these parameters were below 0.20 mg/kg, the lowest dose tested. In another experiment, LC-AmB was compared with Abelcet and showed a better reduction of parasite burden after three injections of 1 mg/kg, but there were not sufficient data to allow ED50 values to be calculated (22). Therefore, we can conclude that this new AmB formulation retains antileishmanial activity in vivo, but it is difficult to position it with respect to other formulations. 

Liposomal amphotericin B (AmBisome) - Administer 3 mg/kg/day on days 1 through 5, 14 and 21 to immunocompetent patients a repeat course of therapy may be useful if parasitic clearance is not achieved. Administer 4 mg/kg/day on days 1 through 5, 10, 17, 24, 31, and 38 to immunosuppressed patients seek expert advice regarding further therapy if parasitic clearance is not achieved. 

No pentavalent antimonial is licensed for use, but sodium stibogluconate is available from the Parasitic Disease Drug Service of the Centers for Disease Control (CDC) for treatment of leishmaniasis. While the pentavalent antimony compounds can be given intravenously or intramuscularly, local infiltration of the lesion in cutaneous leishmaniasis is highly effective. Because of the lower toxicity of liposomal amphotericin B, this drug is considered a first-line choice for vis-cerotropic leishmaniasis rather than the antimonials. 

A. Liposomal amphotericin B was approved by the US. Food and Drug Administration to treat visceral leishmaniasis. Pentavalent antimony compounds, pentamidine, amphotericin B, and aminosi-dine (paromomycin) have all been demonstrated efficacious here. The liposomal amphotericin appears to be better taken up by the reticuloendothelial system, where the parasite resides, and partitions less in the kidney, where amphotericin B traditionally manifests its toxicity. In addition to being better tolerated by patients, it has proved to be very effective in India, where resistance to antimony drugs is widespread. This patient appears to have acquired his infection there, where many infected patients develop darkening of the skin, hence the name kala-azar, or black sickness. Albendazole, an anthelmintic, has no role here. Atovaquone, a naphthoquinone, is used to treat malaria, babesiosis, and pneumocystosis. Pyrimethamine-sulfadoxine is used to treat malaria and toxoplasmosis. Proguanil inhibits the dihydrofolate reductase of malaria parasites and is used in combination with atovaquone. 

Paromomycin sulfate is an aminoglycoside antibiotic that until recently was used in parasitology only for oral therapy of intestinal parasitic infections (see previous text). It has recently been developed for the treatment of visceral leishmaniasis. A phase 3 trial in India showed excellent efficacy for this disease, with a daily intramuscular dosage of 11 mg/kg for 21 days yielding a 95% cure rate, and noninferiority compared with amphotericin. The drug was registered for the treatment of visceral leishmaniasis in India in 2006. In initial studies, paromomycin was well tolerated, with common mild injection pain, uncommon ototoxicity and reversible liver enzyme elevations, and no nephrotoxicity. Paromomycin is much less expensive than liposomal amphotericin or miltefosine, the other promising new therapies for visceral leishmaniasis. 

Date, A., Joshi, M., Patravale, V. Parasitic diseases Liposomes and polymeric nanoparticles versus lipid nanoparticles. Adv. Drug Deliv. Rev. 2007, 59 (6), 505-521. 

Lowik et demonstrated that the secondary structure of certain peptide sequences conjugated to single Ci8 alkyl chains at both the N- and C-termini could be induced upon incorporation into a liposome membrane. A sequence derived from the circumsporozoite (CS) protein of the malaria parasite Plasmodium falciparum was chosen, as within the natural protein the Asn-Pro-Asn-Ala repeat is known to adopt a j6-tum. Both the unmodified peptide in solution and the analogous peptide with only one alkyl chain showed random coil folding characteristics. However, when the double alkylated peptide was inserted into l,2-dimyristoyl-OT-glycero-3-phosphoethanol-amine (DSPC) liposomes the peptide folded into a P-hairpin. This simple approach is a convenient way for stabilizing a variety of peptides into their preferred secondary structure and might be employed in the presentation of multiple (hairpin) epitopes. 

The harmaline (61), isolated from Peganum harmala (Nitrariaceae), exhibits amastigote-specific activity (IC50 of 116 pM). Harmine (62) isolated from same plant species reduces spleen parasite load by approximately 40, 60, 70, and 80% in free, liposomal, niosomal, and nanoparticular forms, respectively, in mice model [87]. 

Staining Applications Lysosomes Golgi apparatus acidic compartments secretory granules (SGs) synap-tic-like microvesicles (SLMVs) ° liposomes acidic organelle membranes bacteria bacterial endo-spores apoptotic ceUs blood smears " nucleic acids cells malignant musculoskeletal tumors micronucleus microorganisms nuclei peptides " proteins antibodies " parasites sperms ... 

Date AA, Joshi MD, Patravale VB. Parasitic diseases liposomes and polymeric nanoparticles versus lipid... 

Imaging/Labeling Applications Golgi apparatus cells liposomes hve malaria blood stage parasites PC-3 prostate cancer ceUs sphingomyelin ... 

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