Endoxifen (EDX) is proven effective in the prevention of ER-positive breast cancer; however, oral administration and subsequent systemic exposure of the drug often cause severe side effects.  To achieve a minimally invasive, localized drug delivery method, a polymeric micellar system, consisting of a poly(e-caprolactone) (PCL) core, a generation 3 (G3) polyester dendron, and a poly(ethylene glycol) (PEG) outer layer, was developed to encapsulate EDX through self-assembly.  The dendron micelles induced substantially enhanced permeation of EDX through both full-thickness mouse (up to 20-fold) and split-thickness human (up to 4-fold) skin samples compared to a traditional chemical penetration enhancer (ethanol).  Stable encapsulation of EDX into the dendron micelles was also demonstrated by a sustained release of drug over 6 days, whereas the cationic liposomes released all EDX within 8 h.  Furthermore, end-groups modification of the dendrons by amination (M-NH2), carboxylation (M-COOH), or acetylation (M-Ac) was shown to affect drug loading and subsequently the skin permeation of EDX.  The in vitro flux of EDX through the skin layers followed the order of M-COOH > M-Ac > M-NH2, which was consistent with the drug loading results.  The effective skin permeation, prolonged drug release, and modular surface functionalities all indicate that the dendron micelles can provide a topical delivery platform for EDX, offering a potential alternative administration route for chemoprevention of breast cancer.

Surface-modified dendron micelles for efficient delivery of endoxifen through mouse and human skin

246th National Meeting (2013)

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