Poloxamine/D-α-Tocopheryl polyethylene glycol succinate (TPGS) mixed micelles and gels: Morphology, loading capacity and skin drug permeability

Abstract The combination of polymeric surfactants with different features into mixed micelles give access to properties that may be superior to the single-component micelles. In this work, we investigated synergistic effects in mixtures of D-α-Tocopheryl polyethylene glycol succinate (TPGS) with poloxamines (also known as Tetronic), pH-responsive and thermogelling polyethylene oxide (PEO)-polypropylene oxide (PPO) 4-arm block copolymers. We examined the morphology of the self-assembled micelles of TPGS with Tetronic 1107 (T1107) and 908 (T908) in the presence of naproxen (NA), used as a model drug, and assessed the capacity of the single and mixed micelles to trap the guest, using a combination of small-angle neutron scattering (SANS) and NMR spectroscopy (1D, 2D-NOESY and diffusion NMR), over a range of compositions and temperatures, in the dilute regime and gel state. NA did not interact with T1107 or T908 in their unimer form, but it was incorporated into the hydrophobic core of the micelles above the critical micellar temperature (CMT). In contrast, TPGS dissolved NA at any temperature, mainly in the tocopherol core, with some partitioning in the PEG-shell. The micellar structure was not altered by the presence of NA, except for an expansion of the core size, a result of the preferential accumulation of NA in that compartment. The solubility of the drug in single component micelles increased markedly with temperature, while mixed micelles produced an intermediate enhancement of the solubility between that of TPGS and the poloxamines, which increased at higher TPGS/poloxamine ratios. Micellar hydrogels formed by the packing of the polymeric mixed micelles in a BCC macrolattice, whose structure was not altered by the presence of the drug (at least at 0.2 wt%). The applicability of the drug-loaded gels for topical formulations was explored by transdermal diffusion testing using a synthetic model of skin, showing that the diffusion of NA across the membrane was enhanced by incorporating small amounts of TPGS to the hydrogel, especially with the more hydrophilic T908.