Block ionomer micellar nanoparticles from double hydrophilic copolymers, classifications and promises for delivery of cancer chemotherapeutics

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A class of double hydrophilic copolymers comprising ionic and nonionic water-soluble blocks, which are also called block ionomers, represent an interesting type of polymer assembly forming stable, homogeneous core-corona dispersions. They exhibit the solution behavior of normal polyelectrolytes, whereas assembly into micelle, vesicle or disk morphology happens by an external stimulus (pH, temperature or ionic strength) or complex formation with metal ions, ionic surfactants, polyelectrolytes, etc. Temperature, pH, redox or salt sensitivity affords a unique opportunity to control the triggered release of payloads accommodated through electrostatic interaction, coordination or chemical conjugation. Moreover, the non-ionic block provides the surface passivation, prolongation of the blood circulation and tumor accumulation, supporting targeted delivery of chemotherapeutic agents based on pathophysiology of tumor microenvironment. Potentiation of antitumor activity, sensitization of the resistant tumors, increased tolerated dose and translation into clinical practice are among their most intriguing characteristics. Their high functionality has been suggested for co-delivery of multiple agents for reversal of chemo-resistance as well as simultaneous therapy and diagnostics. Nevertheless, some stability concerns may be raised due to the polymer disassembly beyond a critical concentration of pH, salt and polyion concentration that can be modulated by introducing crosslinks between the polymer chains (Nano-networks).Graphical abstractPhysicochemical, biological and pharmacological achievements on delivery of chemotherapeutic agents using a class of double hydrophilic polymers named block ionomers whose assembly is induced by external stimuli, complex formation or chemical conjugation is reviewed.

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