Advances in the Structural Design of Polyelectrolyte Complex Micelles

Abstract

Polyelectrolyte complex micelles (PCMs) are a unique class of self-assembled nanoparticles that form with a core of associated polycations and polyanions, microphase-separated from neutral, hydrophilic coronas in aqueous solution. The hydrated nature and structural and chemical versatility make PCMs an attractive system for delivery and for fundamental polymer physics research. By leveraging block copolymer design with controlled self-assembly, fundamental structure–property relationships can be established to tune the size, morphology, and stability of PCMs precisely in pursuit of tailored nanocarriers, ultimately offering storage, protection, transport, and delivery of active ingredients. This perspective highlights recent advances in predictive PCM design, focusing on (i) structure–property relationships to target specific nanoscale dimensions and shapes and (ii) characterization of PCM dynamics primarily using time-resolved scattering techniques. We present several vignettes from these two emerging areas of PCM research and discuss key opportunities for PCM design to advance precision medicine.

Targeted polyelectrolyte complex micelles treat vascular complications in vivo

“…Polyelectrolyte complex micelles are excellent gene-delivery vehicles attributable to their ability to encapsulate charged nucleotides, forming a core by neutralizing the charges via self-assembling, while simultaneously protecting the nucleic acids from nonspecific interactions and enzymatic degradation ( 16 – 18 ). In vivo delivery of therapeutic nucleotides to diseased tissues of interest has often been problematic due to the small size, charge, and instability of the nucleic acid ( 35 ).…”

“…For example, dysregulated miRNA can be corrected by specific mimics/inhibitors ( 7 ). Polyelectrolyte complex micelles have great potential as gene-delivery vehicles due to the ability to encapsulate negatively charged nucleic acids forming a core by neutralizing the charge, while simultaneously protecting the nucleic acids from nonspecific interactions and enzymatic degradation ( 16 , 17 ). Moreover, we demonstrated that polyelectrolyte complex micelles can be functionalized to display small peptides to drive cell-targeting delivery of therapeutic nucleotides ( 18 ).…”

DPD Modelling of the Self- and Co-Assembly of Polymers and Polyelectrolytes in Aqueous Media: Impact on Polymer Science

“…The self-assembly of amphiphilic block copolymers and the co-assembly of double hydrophilic block polyelectrolytes are important phenomena that have been studied by experimentalists, theoreticians and computer scientists for several decades [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Self-and co-assembled nanoparticles find numerous applications in biomedical fields, e.g., as carriers in the targeted delivery of drugs or genes in living organisms, as important agents in radiotherapy and photodynamic therapy and as promising biomarkers and biosensors [14][15][16][17][18][19][20][21][22][23][24][25].…”

Co-Delivery of Synergistic Antimicrobials with Polyelectrolyte Nanocomplexes to Treat Bacterial Biofilms and Lung Infections

“…8,15,35,36 Polyelectrolyte nanocomplexes (NCs) are an emerging class of polymeric nanoparticle drug carrier, and are formed through electrostatic interactions between oppositely charged polymers. 37,38 These NC drug carriers offer physicochemical tunability dependent on the polymer ratios, chemical structures, pKa's, and molecular weights. 37 NCs have further advantages in their ease of fabrication without specialized equipment, and in their high loading efficiencies of therapeutic cargos, especially for drugs of high charge densities, [38][39][40] which often have low encapsulation efficiencies using other polymeric systems.…”

“…37,38 These NC drug carriers offer physicochemical tunability dependent on the polymer ratios, chemical structures, pKa's, and molecular weights. 37 NCs have further advantages in their ease of fabrication without specialized equipment, and in their high loading efficiencies of therapeutic cargos, especially for drugs of high charge densities, [38][39][40] which often have low encapsulation efficiencies using other polymeric systems. 41 However, to our knowledge, no examples of NCs have been reported for the co-delivery of antimicrobials, as NC formulations can be challenging to implement for the co-loading of diverse classes of cargo onto a single drug carrier.…”