Abstract
Delivering active pharmaceutical agents to disease sites using soft polymeric nanoparticles continues to be a topical area of research. It is becoming increasingly evident that the composition of amphiphilic macromolecules plays a significant role in developing efficient nanoformulations. Branched architectures with asymmetric polymeric arms emanating from a central core junction have provided a pivotal venue to tailor their key parameters. The build-up of miktoarm stars offers vast polymer arm tunability, aiding in the development of macromolecules with adjustable properties, and allows facile inclusion of endogenous stimulus-responsive entities. Miktoarm star-based micelles have been demonstrated to exhibit denser coronae, very low critical micelle concentrations, high drug loading contents, and sustained drug release profiles. With significant advances in chemical methodologies, synthetic articulation of miktoarm polymer architecture, and determination of their structure-property relationships, are now becoming streamlined. This is helping advance their implementation into formulating efficient therapeutic interventions. This review brings into focus the important discoveries in the syntheses of miktoarm stars of varied compositions, their aqueous self-assembly, and contributions their formulations are making in advancing the field of drug delivery.
Highlights
A majority of active pharmaceutical agents fail to provide expected relief upon administration as 90% of drugs in the discovery pipeline have very poor water solubility and low bioavailability [1,2,3]
Loading drugs into self-assembled polymeric micelles can help resolve this issue by providing solvation, enabling prolonged gradual release, and through the enhanced permeation and retention (EPR) effect, facilitate passive targeting to disease sites [7,12,117]
Due to a wide range of the hydrophilic fractions (f > 0.45) that conventionally permit amphiphilic polymers to form spherical micelles, and as a result of their simple morphology, micelles constitute the bulk of assemblies that have been explored for drug delivery
Summary
A majority of active pharmaceutical agents fail to provide expected relief upon administration as 90% of drugs in the discovery pipeline have very poor water solubility and low bioavailability [1,2,3]. To achieve a free energy minimum, amphiphilic polymers with distinct hydrophilic and hydrophobic blocks self-assemble in an aqueous medium, into a range of supramolecular structures, including micelles and polymersomes [5,6]. Such nanoparticles can accumulate at disease sites using the enhanced permeation and retention (EPR) effect [7,8,9], resulting from the porous leaky vasculature typical of unhealthy cancerous tissue and its deficient lymphatic drainage [10,11,12]. Poly(2-(dimethylamino)ethyl methacrylate), TIF: Tetraiodofluorescein, TPPBr: Triphenylphosphonium Bromide
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