Enhancing itraconazole Strat-M membrane absorption via biodegradable mixed micelles with platelet-like nanodomains

Various biodegradable or biocompatible polymers have gained significant attention in biomedical and cosmeceutical applications. In this study, we investigated a PEG-PCL-PEG triblock copolymer as a substitute for PEG-PPG-PEG to enhance the solubility and Strat-M membrane permeation of itraconazole (ITZ). The copolymers were characterized by molecular weight, critical micelle concentration (CMC) and micellar size. The resulting micellar formulations were evaluated for particle size, internal structure (vis small-angle X-ray scattering, SAXS), encapsulation efficiency (EE), release behavior, and in vitro Strat-M membrane permeation/deposition. Increasing the hydrophobic/hydrophilic block ratio of copolymers lowered the CMC from 0.044 to 0.016 wt% and increased the size of the plain micellar aggregates from 45.4 to 72.8 nm. In the presence of Tween-80, ITZ loading significantly increased both the particle size and EE of the micellar systems. Additionally, as the hydrophobic/hydrophilic ratio increased, an increase in the particle size and EE of the PEG-PCL-PEG micelles was noted. All ITZ-loaded micellar aggregates with Tween-80 exhibited short-term physical stability during storage at 25 and 37 °C over 24h, with only a modest increase in particle size (up to 1.23-fold) and an essentially unchanged polydispersity index. SAXS analysis suggested that Tween-80 addition drove an internal morphological transition toward more organized, platelet-like domains, with a characteristic d-spacing of 5.3-5.6 nm. All formulations exhibited a release pattern consistent with an initial rapid phase followed by a slower, sustained phase, with the overall release rate decreasing as the hydrophobic/hydrophilic ratio increased. In vitro Strat-M membrane permeation/deposition studies demonstrated that PEG-PCL-PEG micellar aggregates enhanced ITZ transport relative to PEG-PPG-PEG. These results indicate that PEG-PCL-PEG/Tween-80 mixed micelles represent a promising platform for improving topical delivery of hydrophobic drugs.