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

Abstract

The reverse micelle self-assembly of lipophile-functionalized poly(ethylene glycol) (PEG) dendrimer hybrids is probed for applications in carrier-mediated transdermal drug delivery. Under investigation are topologically diverse amphiphiles featuring controlled branching motifs at either the polymer core (one-, two-, and four-arm PEG) and the polar/nonpolar interface (peripheral dendritic generations 0-2). Thus, a systematic investigation of the effect of branching location (core vs peripheral) on carrier properties is described. Dye-encapsulation experiments verify these materials are capable of forming well-defined aggregates and solubilizing polar compounds. Further quantification of reverse micelle critical micelle concentration and dye loading capacity for the branched amphiphile library was obtained through spectroscopy characterization. Both core and peripheral branching are shown to significantly influence dynamic encapsulation behavior, with evidence of location-based contributions extending beyond multiplicity of branching alone. Finally, the in vitro transdermal diffusion of the reverse micelle carriers was investigated through Franz diffusion cell experiments using physiologically relevant juvenile porcine dermis. The permeation results, combined with previously reported aggregate size trends, show the complex relationship between polymer branching and transdermal transport, with the lowest core- and highest peripherally-branched amphiphilic analogs exhibiting optimal transdermal permeation characteristics for this set of branched carriers.

Transdermal Delivery of Therapeutic Compounds With Nanotechnological Approaches in Psoriasis

“…Further skin diffusion studies have demonstrated that in terms of skin permeation, the amphoteric emulsifiers were superior to non-ionic surfactants, but inferior to anionic emulsifiers ( Karande et al, 2005 ; Pham et al, 2016 ). In addition, different patterns of drug release from micelles have been proposed to be dependent on the loading method and drug location; e.g., drugs loaded by physical entrapment or located in the shell/interface are released by diffusion, while drugs loaded by chemical conjugation or located in the center are released by micelle degradation or surface erosion ( Kosakowska et al, 2018 ; Supasena et al, 2020 ).…”

PEG Graft Polymer Carriers of Antioxidants: In Vitro Evaluation for Transdermal Delivery

“…Franz chambers, a popular method for measuring the diffusion rates, were used to determine substance permeation released from the carrier through a membrane imitating artificial skin in a PBS environment [29]. The Franz diffusion cell test enabled the in vitro evaluation of polymeric enteric nanoparticles as the dermal carriers with pH-dependent targeting potential [30], or the assessment of the reverse micelle of lipophile-functionalized PEG dendrimer hybrids for applications in carrier-mediated transdermal drug delivery [31]. Therefore, Franz diffusion cells were also selected to evaluate the permeation through the membrane of the studied micellar carriers and conjugates.…”

Supramolecular Functionalizable Linear–Dendritic Block Copolymers for the Preparation of Nanocarriers by Microfluidics

“…In a similar way, Sierra and coworkers have described plitidepsin nanocarriers [29]. Grayson and coworkers have also explored different branched macromolecular architectures based on PEG and bis-MPA dendrons with fatty acid chains at the periphery as nanocarriers for transdermal drug delivery [30,31]. In addition to bis-MPA based dendrons, relevant examples can be found with other dendrons, e.g., Amir and coworkers have studied the self-assembly properties of LDBCs with PEG and dendrons prepared by thiol-ene reaction with enzymeresponsive peripheral groups [32,33].…”