Liposomes Incorporating a Plasmodium Amino Acid Sequence Target Heparan Sulfate Binding Sites in Liver

Robertson, Richard T.; Baratta, Janie; Haynes, Sherry M.; Longmuir, Kenneth J.

doi:10.1002/jps.21211

Cited by 24 publications

(25 citation statements)

References 43 publications

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“…Then, 3 µl of plasma was diluted to 1.0 ml with PBS, and the 488 Dylight and the Bodipy-TRX emission spectra recorded digitally using a Varian Eclipse spectrofluorometer. The rate of clearance of the long-circulating liposomes is known from our previous work (Longmuir et al 2006Robertson et al 2008), and this slow rate of blood clearance (approximately 5 %/h) of red-labeled liposomes was used as a reference against which the measurements of the green Dylight 488-labeled lectin were compared.…”

Section: Methodsmentioning

confidence: 99%

Use of labeled tomato lectin for imaging vasculature structures

Robertson

Levine

Haynes

et al. 2014

Histochem Cell Biol

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171

118

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Section: Methodsmentioning

confidence: 99%

Use of labeled tomato lectin for imaging vasculature structures

Robertson

Levine

Haynes

et al. 2014

Histochem Cell Biol

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171

118

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“…Liposomes bearing cell-specific recognition ligands on their surfaces have been widely considered as drug carriers in therapy [18,19], and liposome encapsulation has been assayed for the targeted delivery of compounds against murine malaria [20-22]. Liposomal nanovessels incorporating a P. berghei amino acid sequence have been shown to greatly increase their targeting to the liver [23,24], suggesting that they can be an adequate vector to channel antimalarials towards the hepatocyte stages of the parasite.…”

Section: Introductionmentioning

confidence: 99%

Study of the efficacy of antimalarial drugs delivered inside targeted immunoliposomal nanovectors

et al. 2011

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Paul Ehrlich's dream of a 'magic bullet' that would specifically destroy invading microbes is now a major aspect of clinical medicine. However, a century later, the implementation of this medical holy grail continues being a challenge in three main fronts: identifying the right molecular or cellular targets for a particular disease, having a drug that is effective against it, and finding a strategy for the efficient delivery of sufficient amounts of the drug in an active state exclusively to the selected targets. In a previous work, we engineered an immunoliposomal nanovector for the targeted delivery of its contents exclusively to Plasmodium falciparum-infected red blood cells [pRBCs]. In preliminary assays, the antimalarial drug chloroquine showed improved efficacy when delivered inside immunoliposomes targeted with the pRBC-specific monoclonal antibody BM1234. Because difficulties in determining the exact concentration of the drug due to its low amounts prevented an accurate estimation of the nanovector performance, here, we have developed an HPLC-based method for the precise determination of the concentrations in the liposomal preparations of chloroquine and of a second antimalarial drug, fosmidomycin. The results obtained indicate that immunoliposome encapsulation of chloroquine and fosmidomycin improves by tenfold the efficacy of antimalarial drugs. The targeting antibody used binds preferentially to pRBCs containing late maturation stages of the parasite. In accordance with this observation, the best performing immunoliposomes are those added to Plasmodium cultures having a larger number of late form-containing pRBCs. An average of five antibody molecules per liposome significantly improves in cell cultures the performance of immunoliposomes over non-functionalized liposomes as drug delivery vessels. Increasing the number of antibodies on the liposome surface correspondingly increases performance, with a reduction of 50% parasitemia achieved with immunoliposomes encapsulating 4 nM chloroquine and bearing an estimated 250 BM1234 units. The nanovector prototype described here can be a valuable platform amenable to modification and improvement with the objective of designing a nanostructure adequate to enter the preclinical pipeline as a new antimalarial therapy.

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“…It has been demonstrated that conserved peptide sequences (known as region I and II) within the CS are crucial for its targeting capabilities [80]. Attachment of an amino acid sequence derived from region I of CS from P. berghei to the surface of lipid-PEG bioconjugate liposomes resulted in selective targeting of liposomes to heparin sulfate proteo glycans located in the liver [81] and a 15-fold increase in hepatocyte uptake [82]. Similarly, the addition of a short peptide (WIFPWIQL) that recognizes the molecular chaperone BiP/GRP78 in cancerous human umbilical vein endothelial cells to the surface of PEGylated liposome produced a fourfold increase in liposomal uptake by human umbilical vein endothelial cells [83].…”

Section: Targeted Pegylated Liposomesmentioning

confidence: 99%

Properties, Engineering and Applications of Lipid-Based Nanoparticle Drug-Delivery Systems: Current Research and Advances

Buse

El‐Aneed²

2010

Nanomedicine

103

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Lipid-based drug-delivery systems have evolved from micro- to nano-scale, enhancing the efficacy and therapeutic applications of these delivery systems. Production of lipid-based pharmaceutical nanoparticles is categorized into top-down (fragmentation of particulate material to reduce its average total dimensions) and bottom-up (amalgamation of molecules through chemical interactions creating particles of greater size) production methods. Selection of the appropriate method depends on the physiochemical properties of individual entities within the nanoparticles. The production method also influences the type of nanoparticle formulations being produced. Liposomal formulations and solid-core micelles are the most widely utilized lipid-based nanoparticles, with surface modifications improving their therapeutic outcomes through the production of long-circulating, tissue-targeted and/or pH-sensitive nanoparticles. More recently, solid lipid nanoparticles have been engineered to reduce toxicity toward mammalian cells, while multifunctional lipid-based nanoparticles (i.e., hybrid lipid nanoparticles) have been formulated to simultaneously perform therapeutic and diagnostic functions. This article will discuss novel lipid-based drug-delivery systems, outlining the properties and applications of lipid-based nanoparticles alongside their methods of production. In addition, a comparison between generations of the lipid-based nano-formulations is examined, providing insight into the current directions of lipid-based nanoparticle drug-delivery systems.

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Liposomes Incorporating a Plasmodium Amino Acid Sequence Target Heparan Sulfate Binding Sites in Liver

Cited by 24 publications

References 43 publications

Use of labeled tomato lectin for imaging vasculature structures

Use of labeled tomato lectin for imaging vasculature structures

Study of the efficacy of antimalarial drugs delivered inside targeted immunoliposomal nanovectors

Properties, Engineering and Applications of Lipid-Based Nanoparticle Drug-Delivery Systems: Current Research and Advances

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