Controlled Self–Assembly of Non–Linear Amphiphilic Polymers for Therapeutic Drug Delivery Application: Polymer Architecture and the Transdermal Route
Translational research pertains to the areas of scientific exploration and innovation that engenders short-term positive impact on human life and well-being. Toward that end, research of advanced, synthetic polymers present significant translational potential for accessing tailor-made biomaterials of targeted therapeutic functionality. In the present study, the application of amphiphilic polymers as soluble carriers for drug delivery is explored, specifically considering the effect of non-linear polymer architecture in directing physiochemical and therapeutic material performance. To systematically explore structure-property contributions arising from location and extent of polymer branching, a series of lipophile-functionalized poly(ethylene glycol) (PEG) linear-/star-dendrimer hybrids was synthesized. Here, amphiphile topology was controlled by varying the number of branching motifs incorporated at either the polymer core (one-, two- and four-arm PEG) and/or the polar/non-polar interface (peripheral dendritic generations 0 to 2). Material characterization by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS), gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) analysis confirm the well-defined structural and chemical purity of the derived polymer library. As such, the effects of branching location (core versus peripheral) on amphiphilic, reverse micelle self-assembly behavior could be directly probed towards application in carrier-mediated transdermal drug delivery. Physiochemical parameters under investigation include reverse micelle dimensions, stability and payload capacity, with observed architecture-dependent, structure-property contributions further assessed by in vitro transdermal permeation studies. Finally, to demonstrate translational research value, the clinical significance and applications of non-linear polymer carriers in transdermal drug administration is explored.