Synthesis and Self-Assembly of Amphiphilic Star/Linear–Dendritic Polymers: Effect of Core versus Peripheral Branching on Reverse Micelle Aggregation

Abstract

A series of branched polymers, consisting of a poly(ethylene glycol) (PEG) core and lipophilic peripheral dendrons, were synthesized and their self-assembly into reverse micelles studied toward the ultimate goal of carrier-mediated transdermal drug delivery. More specifically, this investigation systematically explores the structure-property contributions arising from location and extent of branching by varying the number of branch points at the core and the generation of dendrons at the polar/nonpolar interface. For branching at the core, PEGs were selected with one, two or four arms, with one terminal functionality per arm. For peripheral branching, end groups were modified with polyester dendrons (of dendritic generations 0, 1, and 2) for each of the three cores. Finally, lauric acid (LA) was used to esterify the periphery, yielding a library of branched, amphiphilic polymers. Characterization of these materials via MALDI-TOF MS, GPC and NMR confirmed their exceptionally well-defined structure. Furthermore, atomic force microscopy (AFM) and dynamic light scattering (DLS) confirmed these polymers' abilities to make discrete aggregates. As expected, increased multiplicity of branching resulted in more compact aggregates; however, the location of branching (core vs periphery) did not seem as important in defining aggregate size as the extent of branching. Finally, computational modeling of the branched amphiphile series was explored to elucidate the macromolecular interactions governing self-assembly in these systems.

Evaluation of Amphiphilic Star/Linear–Dendritic Polymer Reverse Micelles for Transdermal Drug Delivery: Directing Carrier Properties by Tailoring Core versus Peripheral Branching

“…Branched amphiphiles were synthesized as reported elsewhere. 31 Proflavine hemisulfate salt (proflavine HS) was purchased from Millipore-Sigma (St. Louis, MO). 6-Diamidino-2phenylindole (DAPI), phosphate buffered saline (PBS), formalin (1:10 dilution, buffered), sucrose, and all solvents were purchased from Fisher Scientific Inc. (Hampton, NH); materials were used without further purification.…”

A Review of Polymeric Micelles and Their Applications

“…The hydrophilic and hydrophobic parts will interact strongly with polar and non-polar solvents, respectively. Inverse micelles are formed from branched macromolecules [72], water-soluble dendritics [73,74], star-shaped polymers [75,76], and hyperbranched polymers [77,78].…”

The Martini Model in Materials Science

“…A large body of work has investigated the self‐assembly of different block copolymers in water or other solvents [ 123–136 ] Among these systems, the most studied with Martini are poloxamers [ 32,56,137–144 ] also known as pluronics, which are PEO–PPO–PEO amphiphilic triblock copolymers. Such polymers can form a wide range of aggregates ranging from bilayers, over micelles, to polymersomes, that is, synthetic vesicles, the latter ones being particularly studied for applications as nanocarrier devices for drug delivery.…”