Abstract
Poloxamers, also known as Pluronics®, are block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character and useful association and adsorption properties emanating from this. Poloxamers find use in many applications that require solubilization or stabilization of compounds and also have notable physiological properties, including low toxicity. Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current challenges facing nanomedicine revolve around the transport of typically water-insoluble drugs throughout the body, followed by targeted delivery. Judicious design of drug delivery systems leads to improved bioavailability, patient compliance and therapeutic outcomes. The rich phase behavior (micelles, hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to multiple types of processing and various product forms. In this review, we first present the general solution behavior of poloxamers, focusing on their self-assembly properties. This is followed by a discussion of how the self-assembly properties of poloxamers can be leveraged to encapsulate drugs using an array of processing techniques including direct solubilization, solvent displacement methods, emulsification and preparation of kinetically-frozen nanoparticles. Finally, we conclude with a summary and perspective.
Highlights
Poloxamers, available under the trademark Pluronics® (BASF), are a class of water-soluble nonionic A-B-A and B-A-B triblock copolymers, where A is poly(ethylene oxide) (PEO) and B is poly(propylene oxide) (PPO)
These include: Direct solubilization, where simple aqueous or aqueous-organic solvent mixtures including drug and poloxamer result in encapsulation of the drug in poloxamer micelles; thin film methods, where drug-poloxamer mixtures are stabilized in a dried film structure, which can be rehydrated at the time of administration; and temperature-induced emulsification, where emulsions are formed at elevated temperatures and rapidly cooled
The unimer-to-micelle transition of poloxamers is useful in the preparation of kinetically-frozen drug-loaded nanoparticles with high drug loading
Summary
Poloxamers, available under the trademark Pluronics® (BASF), are a class of water-soluble nonionic A-B-A and B-A-B triblock copolymers, where A is poly(ethylene oxide) (PEO) and B is poly(propylene oxide) (PPO). While nano-sized drug vehicles may benefit from the enhanced permeability and retention (EPR) effect, where therapeutics can enter tumors via leaky blood vessels, median delivery efficiencies remain less than 1% [29] This motivates further work in the development of drug carriers with better targeting. The diverse range of potential delivery methods is highlighted in this review by discussing how the poloxamer solution behavior enables multiple formulation processing routes, drug-encapsulating structures, and engagement with physiological barriers to drug passage. There is a large number of functional block copolymers being evaluated for drug carriers [34,35,36] Some of these are responsive to stimuli including ultrasound and pH, depending on the target. A generalized method is reviewed to prepare poloxamer-stabilized drug-loaded nanoparticles with high drug-to-excipient ratios
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