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Electrodelivery of drugs into cancer cells in the presence of poloxamer 188.

Tsoneva I, Iordanov I, Berger AJ, Tomov T, Nikolova B, Mudrov N, Berger MR - J. Biomed. Biotechnol. (2010)

Bottom Line: In the present study it is shown that poloxamer 188, added before or immediately after an electrical pulse used for electroporation, decreases the number of dead cells and at the same time does not reduce the number of reversible electropores through which small molecules (cisplatin, bleomycin, or propidium iodide) can pass/diffuse.It was suggested that hydrophobic sections of poloxamer 188 molecules are incorporated into the edges of pores and that their hydrophilic parts act as brushy pore structures.The formation of brushy pores may reduce the expansion of pores and delay the irreversible electropermeability.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria. itsoneva@obzor.bio21.bas.bg

ABSTRACT
In the present study it is shown that poloxamer 188, added before or immediately after an electrical pulse used for electroporation, decreases the number of dead cells and at the same time does not reduce the number of reversible electropores through which small molecules (cisplatin, bleomycin, or propidium iodide) can pass/diffuse. It was suggested that hydrophobic sections of poloxamer 188 molecules are incorporated into the edges of pores and that their hydrophilic parts act as brushy pore structures. The formation of brushy pores may reduce the expansion of pores and delay the irreversible electropermeability. Tumors were implanted subcutaneously in both flanks of nude mice using HeLa cells, transfected with genes for red fluorescent protein and luciferase. The volume of tumors stopped to grow after electrochemotherapy and the use of poloxamer 188 reduced the edema near the electrode and around the subcutaneously growing tumors.

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Altered haemolysis after the application of one rectangular pulse of 3 kV  ·  cm−1 and duration 0.5 ms in the presence of 10 μM poloxamer 188. +P188 indicates that erythrocytes were electroporated in the presence of 10 μM P188, and +/P188 (10 μM) indicates the addition of P188 after the electrical pulse.
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fig5: Altered haemolysis after the application of one rectangular pulse of 3 kV · cm−1 and duration 0.5 ms in the presence of 10 μM poloxamer 188. +P188 indicates that erythrocytes were electroporated in the presence of 10 μM P188, and +/P188 (10 μM) indicates the addition of P188 after the electrical pulse.

Mentions: The kinetics of haemolysis after application of one rectangular pulse of 3 kV · cm−1 (duration of 0.5 ms) in the presence of a very low concentration of P188 (10 μM) is shown in Figure 5. Each point reflects the ratio between electroporated erythrocytes (erythrocytes alone, in the presence of P188 or P188 is added after electroporation) and erythrocytes haemolysed by distillated water (100% lysis). The percentage of erythrocytes haemolysed within one hour was 40% and reached 95% after 5 hours. When electroporation was done in the presence of P188, haemolysis after one hour was 22% and after 5 hours 60%, while when P188 was added after the electrotreatment the extent of haemolysis was 38% after one hour and reached a plateau of about 60% after 2 hours. The protective effect of P188 was less clear if the compound was added after electroporation, however after 5 hours the extent of haemolysis was 60% for both exposure modalities (Figure 5).


Electrodelivery of drugs into cancer cells in the presence of poloxamer 188.

Tsoneva I, Iordanov I, Berger AJ, Tomov T, Nikolova B, Mudrov N, Berger MR - J. Biomed. Biotechnol. (2010)

Altered haemolysis after the application of one rectangular pulse of 3 kV  ·  cm−1 and duration 0.5 ms in the presence of 10 μM poloxamer 188. +P188 indicates that erythrocytes were electroporated in the presence of 10 μM P188, and +/P188 (10 μM) indicates the addition of P188 after the electrical pulse.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2913842&req=5

fig5: Altered haemolysis after the application of one rectangular pulse of 3 kV · cm−1 and duration 0.5 ms in the presence of 10 μM poloxamer 188. +P188 indicates that erythrocytes were electroporated in the presence of 10 μM P188, and +/P188 (10 μM) indicates the addition of P188 after the electrical pulse.
Mentions: The kinetics of haemolysis after application of one rectangular pulse of 3 kV · cm−1 (duration of 0.5 ms) in the presence of a very low concentration of P188 (10 μM) is shown in Figure 5. Each point reflects the ratio between electroporated erythrocytes (erythrocytes alone, in the presence of P188 or P188 is added after electroporation) and erythrocytes haemolysed by distillated water (100% lysis). The percentage of erythrocytes haemolysed within one hour was 40% and reached 95% after 5 hours. When electroporation was done in the presence of P188, haemolysis after one hour was 22% and after 5 hours 60%, while when P188 was added after the electrotreatment the extent of haemolysis was 38% after one hour and reached a plateau of about 60% after 2 hours. The protective effect of P188 was less clear if the compound was added after electroporation, however after 5 hours the extent of haemolysis was 60% for both exposure modalities (Figure 5).

Bottom Line: In the present study it is shown that poloxamer 188, added before or immediately after an electrical pulse used for electroporation, decreases the number of dead cells and at the same time does not reduce the number of reversible electropores through which small molecules (cisplatin, bleomycin, or propidium iodide) can pass/diffuse.It was suggested that hydrophobic sections of poloxamer 188 molecules are incorporated into the edges of pores and that their hydrophilic parts act as brushy pore structures.The formation of brushy pores may reduce the expansion of pores and delay the irreversible electropermeability.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria. itsoneva@obzor.bio21.bas.bg

ABSTRACT
In the present study it is shown that poloxamer 188, added before or immediately after an electrical pulse used for electroporation, decreases the number of dead cells and at the same time does not reduce the number of reversible electropores through which small molecules (cisplatin, bleomycin, or propidium iodide) can pass/diffuse. It was suggested that hydrophobic sections of poloxamer 188 molecules are incorporated into the edges of pores and that their hydrophilic parts act as brushy pore structures. The formation of brushy pores may reduce the expansion of pores and delay the irreversible electropermeability. Tumors were implanted subcutaneously in both flanks of nude mice using HeLa cells, transfected with genes for red fluorescent protein and luciferase. The volume of tumors stopped to grow after electrochemotherapy and the use of poloxamer 188 reduced the edema near the electrode and around the subcutaneously growing tumors.

Show MeSH
Related in: MedlinePlus