Crosslinked hybrid micellar platform for targeted cutaneous drug delivery.

Micellar systems are transformed upon contact with the stratum corneum lipids, disassembling and releasing their cargo. Thus, the development of micellar systems for sustained cutaneous delivery that retain structural integrity poses considerable challenges. Herein, a highly stable crosslinked hybrid micellar (cHy-Micelles) platform is developed for controlled cutaneous drug delivery. The amine functionalized N-(2-aminoethyl)pentacosa-10,12-diynamide (AMP-1) was synthesized first; then, hybrid micelles were prepared by mixing it with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) using nanoprecipitation. The micelles were stabilized by UV light irradiation and then characterized to determine morphology, stability, and ability to deliver a cargo. The spherical cHy-micelles with < 50 nm size (37.84 ± 0.45 nm) were highly stable and monodispersed (polydispersity index 0.099 ± 0.004) in the final hydrogel formulation because of intermolecular crosslinking within the micelle. These cHy-micelles also showed excellent cutaneous retention ability and low skin permeation owing to the positive surface potential (ζ potential +42 ± 7.15 mV) - skin has an isoelectric point (pI) of 4-4.5. Interestingly, the targeted cutaneous delivery of poorly water-soluble rose bengal, itraconazole, and clotrimazole was achieved using the developed micelles without showing significant transdermal permeation. This new crosslinked hybrid micellar platform could have enormous potential for topical drug delivery since it could enable modified kinetics as compared to conventional micelles, whilst decreasing the risk of systemic side effects.