Lipid-like trifunctional block copolymers of ethylene oxide and propylene oxide: effective and cytocompatible modulators of intracellular drug delivery.
A new glycerol-based trifunctional block copolymer (TBC) of propylene oxide and ethylene oxide and its conjugate with succinic acid (TBC-SA) were studied as a drug delivery system and compared with Pluronic L61. TBCs have multiple effects on the plasma membrane of human cells, e.g. increasing its fluidity and ion permeability, inhibiting ATPase activity of efflux transporter P-glycoprotein through reversible membrane destabilization. Such membrane-modulating properties attributed to the unimer form of copolymers increase in the order Pluronic L61≪TBC<TBC-SA and correlate with an ability of TBCs to promote the accumulation of P-glycoprotein substrates in lung cancer A549 cells. Furthermore, TBC, and especially TBC-SA, exhibit substantially lower hemolytic, cytotoxic and proapoptotic activities in comparison with Pluronic L61. Our results demonstrate that TBCs are promising analogs of bifunctional Pluronics in anticancer drug delivery.
Kazan (Volga Region) Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia.
Oksana V
OV
Bondar
Kazan (Volga Region) Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia.
Yuriy V
YV
Badeev
Kazan (Volga Region) Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia.
Yurii G
YG
Shtyrlin
Kazan (Volga Region) Federal University, 18 Kremlyovskaya Street, 420008 Kazan, Russia. Electronic address: tabdulli@gmail.com.
Timur I
TI
Abdullin
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004852:Epoxy Compounds / Q000737:chemistry*; D005027:Ethylene Oxide / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010539:Permeability; D020442:Poloxamer / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D019802:Succinic Acid / Q000737:chemistry*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004337:Drug Carriers; D004852:Epoxy Compounds; D011108:Polymers; C480965:pluronic L61; D020442:Poloxamer; D019802:Succinic Acid; D000251:Adenosine Triphosphatases; D005027:Ethylene Oxide; C009068:propylene oxide
Anticancer drugs; Intracellular drug delivery; Membrane modulators; Multidrug resistance; P-glycoprotein; Trifunctional block copolymers of ethylene oxide and propylene oxide