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

Urbán P, Estelrich J, Adeva A, Cortés A, Fernàndez-Busquets X - Nanoscale Res Lett (2011)

Bottom Line: The results obtained indicate that immunoliposome encapsulation of chloroquine and fosmidomycin improves by tenfold the efficacy of antimalarial drugs.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Nanobioengineering Group, Institute for Bioengineering of Catalonia, Baldiri Reixac 10-12, Barcelona, E08028, Spain. xfernandez_busquets@ub.edu.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Cryo-TEM images of liposomes.
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Figure 3: Cryo-TEM images of liposomes.

Mentions: For immunoliposome assembly, different lipid combinations had been tested in order to establish a formulation with low hemolytic activity and low general cytotoxicity, which is DOPC/cholesterol/MPB-PE 77.5:20:2.5 [25]. Liposomes formed in this way were stable and generally did not coalesce even after high-speed centrifugation (Figure 3A), but occasionally, fusion events were observed (Figure 3B). Although dynamic light scattering analysis indicated that the liposome population had a mean diameter of 200 nm and a lower limit of 100 nm, TEM images showed a significant number of smaller liposomes down to 50 nm across. Most liposomes were unilamellar but a substantial fraction of them (about 10%) were enclosed by two or more lipid bilayers.


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

Urbán P, Estelrich J, Adeva A, Cortés A, Fernàndez-Busquets X - Nanoscale Res Lett (2011)

Cryo-TEM images of liposomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285703&req=5

Figure 3: Cryo-TEM images of liposomes.
Mentions: For immunoliposome assembly, different lipid combinations had been tested in order to establish a formulation with low hemolytic activity and low general cytotoxicity, which is DOPC/cholesterol/MPB-PE 77.5:20:2.5 [25]. Liposomes formed in this way were stable and generally did not coalesce even after high-speed centrifugation (Figure 3A), but occasionally, fusion events were observed (Figure 3B). Although dynamic light scattering analysis indicated that the liposome population had a mean diameter of 200 nm and a lower limit of 100 nm, TEM images showed a significant number of smaller liposomes down to 50 nm across. Most liposomes were unilamellar but a substantial fraction of them (about 10%) were enclosed by two or more lipid bilayers.

Bottom Line: The results obtained indicate that immunoliposome encapsulation of chloroquine and fosmidomycin improves by tenfold the efficacy of antimalarial drugs.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Nanobioengineering Group, Institute for Bioengineering of Catalonia, Baldiri Reixac 10-12, Barcelona, E08028, Spain. xfernandez_busquets@ub.edu.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus