Dissolving microneedles enable effective transdermal delivery of vitamin B12 and reduce endothelial inflammation

Abstract

Vitamin B12 deficiency is a significant clinical concern, often leading to pernicious anaemia and associated vascular dysfunction. Traditional supplementation methods face challenges such as poor absorption in patients lacking intrinsic factor, highlighting the need for alternative delivery strategies. This study investigates the use of dissolving microneedles for transdermal delivery of vitamin B12, evaluating both permeation efficiency and biological effects on endothelial cells. Microneedle arrays were fabricated using polyvinyl pyrrolidone (PVP K30) combined with either 7.5% or 15% trehalose dihydrate at two needle lengths (800 µM and 900 µM). Following mechanical characterisation, the optimal formulation and needle length were applied to excised murine skin in a Franz diffusion cell system to assess vitamin B12 permeation. Receiver media were collected and applied to EA.hy926 endothelial cells to evaluate trans-endothelial permeation and the effect of permeated B12 on TNF-α-induced inflammation by measuring IL-6 expression and reactive oxygen species (ROS) generation. Microneedles composed of PVP K30 with 15% trehalose at 900 µM length demonstrated superior mechanical properties and insertion efficiency. The Franz cell study revealed that over 24 hours, approximately 25% of vitamin B12 permeated through murine skin. The permeated vitamin B12 efficiently traversed the endothelial cell barrier in vitro within 1.5 hours and significantly suppressed TNF-α-induced IL-6 expression and ROS production in EA.hy926 cells. These findings suggest that PVP-trehalose dissolving microneedles provide a promising transdermal delivery platform for vitamin B12, capable of sustained release and effective biological activity. This approach holds potential as a minimally invasive treatment option for pernicious anaemia and related vascular complications.