Pluronic block copolymers: Evolution of drug delivery concept from inert nanocarriers to biological response modifiers

Abstract

Polymer nanomaterials have sparked a considerable interest as vehicles used for diagnostic and therapeutic agents; research in nanomedicine has not only become a frontier movement but is also a revolutionizing drug delivery field. A common approach for building a drug delivery system is to incorporate the drug within the nanocarrier that results in increased solubility, metabolic stability, and improved circulation time. With this foundation, nanoparticles with stealth properties that can circumvent RES and other clearance and defense mechanisms are the most promising. However, recent developments indicate that select polymer nanomaterials can implement more than only inert carrier functions by being biological response modifiers. One representative of such materials is Pluronic block copolymers that 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 and affecting various cellular functions, such as mitochondrial respiration, ATP synthesis, activity of drug efflux transporters, apoptotic signal transduction, 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 causes transcriptional activation of gene expression both in vitro and in vivo. Collectively, these studies suggest that Pluronics have a broad spectrum of biological response modifying activities which make it one of the most potent drug targeting systems available, resulting in a remarkable impact on the emergent field of nanomedicine.

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

“…A balance between hydrophobic and hydrophilic contribution has been shown to be critical for the functioning of many amphiphilic compounds and as a determining parameter for their transfection efficiency, for example, for the pluronics block copolymers. 33 In this study, we establish a parallel between the importance of this equilibrium and that of the symmetry between the contributions to DNA binding by the two different components of lipospermines. Thus, interaction of butanoylspermine with pDNA is close to a pure cationic interaction.…”

Study on uptake of PLA-Pluronic P85-PLA nanoparticles with Caco-2 cells

“…Pluronics consisting of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) (PEO-PPO-PEO) can assemble into micelles, with the PPO blocks forming a hydrophobic core and the PEO blocks the surrounding hydrophilic corona in solution [2]. Several PEO-PPO-PEO block copolymers are widely used for several routes of administration for drug delivery, and have been reported to be a promising way to improve the oral bioavailability of peptides and proteins [2,3].…”

Stabilized micelles as delivery vehicles for paclitaxel

“…On the other hand, drug encapsulation in micelles can diminish drug extravasation to normal tissues and provide a passive drug targeting to tumors via the enhanced permeability and retention effect (EPR) (Maeda et al, 2000). This increased permeability is favorised by the prolonged circulation of micelles and lack of renal clearance (Han et al, 2006;Batrakova et al, 2008). On the other hand, Pluronic copolymers (as other pharmaceutical excipients) may inhibit the activity of drug efflux transporters such as P-gp, MRPs and BCRP Thomas et al, 2003;Huang et al, 2008).…”