Despite the multiplicity of factors that regulate transdermal permeability, transport investigations to date have focused predominantly on solute molecular weight and extracellular matrix compatibility, rather than membrane properties of the skin itself. The present study aims to establish the size-dependent restrictions of dermal flux using dendrimer-based probes of discrete sizes and corresponding lipophilicity to assess the permeability of the “brick-and-mortar assembly” of the <i>stratum corneum</i>. The unique material properties of dendrimer particles—namely, monodisperse, compact structures with tunable size and high surface functionality allowing tailored design—afford modular access to a comprehensive range of well-defined probe sizes. 2,2-Bis(hydroxymethyl)propionic acid (bisMPA)-based polyester scaffolds were synthesized from tris- and tetra-functional cores over dendritic generations (layers of branched monomers) G0 through G3 and conjugated to a single Rhodamine B fluorophore. Comprehensive surface esterification of remaining surface alcohols was carried out using lauric (C12) acid to impart the requisite lipid solubility for transdermal transport. Thus, a library of monodisperse, hydrophobic probes was readily generated, featuring covalently-bound tags to allow for spectroscopic monitoring independent of aggregation or encapsulation phenomena. Material characterization by MALDI-TOF MS, NMR and GPC as well as physical characterization by emission spectroscopy and DLS confirm the well-defined nature of derived constructs. By this means, transdermal permeability as a function of size was assessed in vitro with a juvenile porcine dermis model using Franz diffusion cell apparatus.

Dendrimer-based probes for investigating size restrictions of transdermal permeability

255th National Meeting (2018)

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