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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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Related in: MedlinePlus

Flow cytometry of MDA-MB-231 cells. Experimental conditions: 5 · 105 cells per 100 μl suspension of 0.3 M mannitol, 0.1 mM Ca acetate and 0.1 mM Mg acetate. Field strength—1.0 kV  ·  cm−1, one pulse with a duration of 5 ms. 100 μM propidium iodide (PI) was added during the pulse or after it; (a) nonporated control with PI added; (b) porated control with PI added before the pulse; (c) porated control with PI added after the pulse; (d) and (e)  0.1 mM, (f) and (g) 0.5 mM, (h) and (i) 1.0 mM poloxamer 188 and 100 μM PI added; (d), (f) and (h) are samples electroporated in the presence of poloxamer 188 and PI; (e), (g) and (i) poloxamer 188 and PI were added after the pulse. The M1-marker represents the nonpermeable cells and the M2-marker—the permeable cells.
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fig2: Flow cytometry of MDA-MB-231 cells. Experimental conditions: 5 · 105 cells per 100 μl suspension of 0.3 M mannitol, 0.1 mM Ca acetate and 0.1 mM Mg acetate. Field strength—1.0 kV · cm−1, one pulse with a duration of 5 ms. 100 μM propidium iodide (PI) was added during the pulse or after it; (a) nonporated control with PI added; (b) porated control with PI added before the pulse; (c) porated control with PI added after the pulse; (d) and (e) 0.1 mM, (f) and (g) 0.5 mM, (h) and (i) 1.0 mM poloxamer 188 and 100 μM PI added; (d), (f) and (h) are samples electroporated in the presence of poloxamer 188 and PI; (e), (g) and (i) poloxamer 188 and PI were added after the pulse. The M1-marker represents the nonpermeable cells and the M2-marker—the permeable cells.

Mentions: The electropermeabilisation was followed by flow cytometry measurements with PI [31]. The dye was added at 100 μM concentration to the cell suspension containing 5 · 105 cells (12 · 109 PI molecules per cell). The fraction of electropermeabilised cells is the percentage within the M2 marker (Figures 2–4).


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)

Flow cytometry of MDA-MB-231 cells. Experimental conditions: 5 · 105 cells per 100 μl suspension of 0.3 M mannitol, 0.1 mM Ca acetate and 0.1 mM Mg acetate. Field strength—1.0 kV  ·  cm−1, one pulse with a duration of 5 ms. 100 μM propidium iodide (PI) was added during the pulse or after it; (a) nonporated control with PI added; (b) porated control with PI added before the pulse; (c) porated control with PI added after the pulse; (d) and (e)  0.1 mM, (f) and (g) 0.5 mM, (h) and (i) 1.0 mM poloxamer 188 and 100 μM PI added; (d), (f) and (h) are samples electroporated in the presence of poloxamer 188 and PI; (e), (g) and (i) poloxamer 188 and PI were added after the pulse. The M1-marker represents the nonpermeable cells and the M2-marker—the permeable cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Flow cytometry of MDA-MB-231 cells. Experimental conditions: 5 · 105 cells per 100 μl suspension of 0.3 M mannitol, 0.1 mM Ca acetate and 0.1 mM Mg acetate. Field strength—1.0 kV · cm−1, one pulse with a duration of 5 ms. 100 μM propidium iodide (PI) was added during the pulse or after it; (a) nonporated control with PI added; (b) porated control with PI added before the pulse; (c) porated control with PI added after the pulse; (d) and (e) 0.1 mM, (f) and (g) 0.5 mM, (h) and (i) 1.0 mM poloxamer 188 and 100 μM PI added; (d), (f) and (h) are samples electroporated in the presence of poloxamer 188 and PI; (e), (g) and (i) poloxamer 188 and PI were added after the pulse. The M1-marker represents the nonpermeable cells and the M2-marker—the permeable cells.
Mentions: The electropermeabilisation was followed by flow cytometry measurements with PI [31]. The dye was added at 100 μM concentration to the cell suspension containing 5 · 105 cells (12 · 109 PI molecules per cell). The fraction of electropermeabilised cells is the percentage within the M2 marker (Figures 2–4).

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