Pluronics and MDR Reversal: An Update

Abstract

Multidrug resistance (MDR) remains one of the biggest obstacles for effective cancer therapy. Currently there are only few methods that are available clinically that are used to bypass MDR with very limited success. In this review we describe how MDR can be overcome by a simple yet effective approach of using amphiphilic block copolymers. Triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), arranged in a triblock structure PEOPPO-PEO, Pluronics or “poloxamers”, raised a considerable interest in the drug delivery field. Previous studies demonstrated that Pluronics sensitize MDR cancer cells resulting in increased cytotoxic activity of Dox, paclitaxel, and other drugs by 2–3 orders of magnitude. Pluronics can also prevent the development of MDR in vitro and in vivo. Additionally, promising results of clinical studies of Dox/Pluronic formulation reinforced the need to ascertain a thorough understanding of Pluronic effects in tumors. These effects are extremely comprehensive and appear on the level of plasma membranes, mitochondria, and regulation of gene expression selectively in MDR cancer cells. Moreover, it has been demonstrated recently that Pluronics can effectively deplete tumorigenic intrinsically drug-resistant cancer stem cells (CSC). Interestingly, sensitization of MDR and inhibition of drug efflux transporters is not specific or selective to Pluronics. Other amphiphilic polymers have shown similar activities in various experimental models. This review summarizes recent advances of understanding the Pluronic effects in sensitization and prevention of MDR.

Reversion of multidrug resistance by a pH-responsive cyclodextrin-derived nanomedicine in drug resistant cancer cells

“…According to the average molecular weight of 1380 Da, Ac-aCD NP of 0.05, 0.5, 5, 50, and 500 µg/mL corresponds to 0.036, 0.36, 3.6, 36, and 360 nmol/mL of Ac-aCD, respectively. Consequently, Ac-aCD NP is effective at Ac-aCD concentrations lower than those of herein examined sensitizers and some previously reported Pgp inhibitors [5,11,26,51,52].…”

“…Nanomedicines can reverse MDR by changing internalization modes of anticancer drugs, varying intracellular release profiles of payload, or co-delivering different MDR modulators with anticancer agents. Besides, a few nanomedicines are able to sensitize MDR cancer cells by suppressing the activity of the MDR efflux pump and the transporters' ATPase, depriving metabolic energy, interacting with lipid membranes and changing their properties, or promoting proapoptotic signaling [8,11]. From the viewpoint of clinical translation, however, challenges remain for these nanomedicines with respect to both effectiveness and safety profiles.…”

Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer

“…Pluronics are triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), arranged in PEO-PPO-PEO structure. They have a core containing PPO blocks, which serves to incorporate hydrophobic drugs (Alakhova & Kabanov, 2014). Pluronic block copolymers are thought to associate with energy metabolism in MDR cancer cells.…”

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

“…Polyvinyl alcohol (PVA) polymer is widely used for NP formulations as well as controlled release dosage forms. Nonionic pluronic surfactants are block copoly m e r s o f p o l y o x y e t h y l e n e s a n d w i c h e d b e t w e e n polyoxypropylene chains [22]. These surfactants have been broadly utilized for biomedical applications including drug delivery, nonfouling, and tissue engineering applications [23][24][25].…”