Inkjet printing of pharmaceutical tattoos for the direct deposition of oestradiol onto skin in turner syndrome

Abstract

Turner syndrome, a rare chromosomal disorder affecting 1 in 2500 females, is characterized by the partial or complete absence of the second X chromosome. The primary treatment involves oestradiol (E2) hormone replacement therapy, essential for inducing puberty and maintaining secondary sex characteristics. While transdermal E2 patches are preferred due to their controlled release and bypassing of first-pass metabolism, paediatric dosing poses significant challenges since patches cannot be safely cut for adjustment. Although a weight-based nocturnal E2 regimen is recommended, achieving precise, personalised dosing is challenging to achieve. This study explores an innovative approach to obtain personalised transdermal doses using a handheld commercial inkjet printer to apply E2 directly onto the skin, in the form of temporary drug-loaded tattoos. A highly soluble (52.24 ± 8.76 mg/mL) E2-loaded pharma-ink was developed using a propylene glycol and ethanol (2:8) formulation. The ink was successfully printed in various designs on both paper and porcine skin, demonstrating excellent resolution and reproducibility. Dose linearity was confirmed (R² > 0.96) with 3.8 ± 0.5 µg of E2 delivered per single printing pass using a 2 mg/mL pharma-ink. Personalised dosing is achievable by altering the concentration of E2 in the ink or by adjusting the number of printing passes, ideal for young Turner syndrome patients who require periodic dose adjustments. In vitro Franz Cell permeation studies revealed a first-order extended permeation profile, with 100 % of E2 permeating within 8 h, supporting nocturnal administration to mimic natural hormone fluctuations during puberty. Handheld inkjet printing therefore offers a novel solution by enabling precise, low-dose delivery of E2 directly onto the skin, making it a promising approach for tailored treatment in young patients with Turner syndrome.

Keywords: 2D printing of pharmaceuticals; Drop on demand inkjet printing; Estradiol; Paediatric pharma-ink tattoos; Rare diseases; Sex-specific formulations; Transdermal delivery.