1.D.68 The Pore-forming Pleuronic Block Polymer (PPBP) Family 

Polymer nanomaterials are vehicles used for diagnostic and therapeutic agents, and research in nanomedicine has revolutionized the drug delivery field. A common approach for building a drug delivery system is to incorporate the drug within a nanocarrier that results in increased solubility, metabolic stability, and improved circulation time. Nanoparticles can circumvent clearance and defense mechanisms. Pluronic block copolymers cause various functional alterations in cells. The key attribute for the biological activity of Pluronics is their ability to incorporate into membranes followed by subsequent translocation into the cells, affecting various cellular functions, such as mitochondrial respiration, ATP synthesis, activity of drug efflux transporters, and gene expression. As a result, Pluronics cause drastic sensitization of MDR tumors to various anticancer agents, enhance drug transport across the blood brain and intestinal barriers, and cause transcriptional activation of gene expression (Batrakova and Kabanov 2008).

Pluronics L64 interacts with a dioleylphosphatidylcholine (DOPC) lipid bilayers. The initial configuration of the polymer with respect to the bilayer determines its final conformation within the bilayer. When the polymer is initially placed at the lipid/water interface, partial insertion of the polymer in a U-shaped conformation is observed, but when the polymer is centered at the bilayer, it stabilizes to a transmembrane state, facilitating water transport across the bilayer (Ileri Ercan et al. 2016). Then, membrane thickness decreases while its fluidity increases. When the polymer concentration inside the bilayer is high, pore formation is initiated. The hydrophilic/lipophilic balance of the polymer plays a critical role in the interaction mechanisms as well as in the dynamics within the bilayer.



Batrakova, E.V. and A.V. Kabanov. (2008). Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release 130: 98-106.

Ileri Ercan, N., P. Stroeve, J.W. Tringe, and R. Faller. (2016). Understanding the Interaction of Pluronics L61 and L64 with a DOPC Lipid Bilayer: An Atomistic Molecular Dynamics Study. Langmuir. [Epub: Ahead of Print]