Electrodelivery of drugs into cancer cells in the presence of poloxamer 188.
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.
Tsoneva
Iana
I
Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria. itsoneva@obzor.bio21.bas.bg
Iordanov
Iordan
I
Berger
Annette J
AJ
Tomov
Toma
T
Nikolova
Biliana
B
Mudrov
Nikola
N
Berger
Martin R
MR
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001761:Bleomycin / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002945:Cisplatin / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D018274:Electroporation / Q000379:methods*; D005434:Flow Cytometry; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D020442:Poloxamer / Q000008:administration & dosage*; D016062:Porosity / Q000187:drug effects; D011419:Propidium; D013050:Spectrometry, Fluorescence; D051598:Whole Body Imaging; D023041:Xenograft Model Antitumor Assays; D000097573:Red Fluorescent Protein
D000970:Antineoplastic Agents; D001761:Bleomycin; D002945:Cisplatin; D008156:Luciferases; D008164:Luminescent Proteins; D020442:Poloxamer; D011419:Propidium; D000097573:Red Fluorescent Protein