Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Non-invasive detection of dermal NAD+ using multiphoton imaging due to nicotinamide mononucleotide loaded microneedles as a possible treatment for aging-related diseases (#122)

Masood MA Ali 1 , Sarika SN Namjoshi 1 , Heather HB Benson 2 , Tushar TK Kumeria 3 , Yousuf YM Mohammed 1
  1. The University of Queensland, Brisbane, QUEENSLAND, Australia
  2. Curtin University, Perth
  3. University of New South Wales, Sydney

Nicotinamide adenine dinucleotide (NAD) is a vital cellular metabolic redox cofactor molecule responsible for various biological enzymatic reactions. Multiple surveillance studies have shown a steady decline in NAD+ levels with age, resulting in altered cellular metabolism and increased disease susceptibility, causing neurodegenerative diseases. Among the NAD+ precursors, nicotinamide mononucleotide (NMN) is a promising precursor that have shown fewer unfavourable side effects. Although available in oral doses, their effect was shown to be variable when compared to intraperitoneal injection. Therefore, the objective of this study was the controlled transdermal delivery of NAD+ precursor molecule NMN using microneedles, and subsequent transdermal NAD+ detection using 2photon microscopy. NMN-µNDs were fabricated using micro-moulding and solvent casting techniques respectively. NMN µNDs consisted of µNDs shaft height of 606.75 ± 37.25 µm, and a base diameter of 369.25 ± 52.75 µm, yielding an aspect ratio (height: base diameter) of approximately 2:1. The µNDs pierced the stratum corneum and into the dermis, causing a puncture depth of 100 ± 48 µm, confirmed by scanning electron microscopy and histology cryo-sectioning, while confocal laser scanning microscopy confirmed the presence of a model dye (rose Bengal) at 180 µm into the human in-vitro skin. In-vitro permeation test (Franz diffusion) on dermatomed donor human skin (thickness 500µm) demonstrated 208 ± 45 µg from 0.3707 mg NMN per µND array and 400 ± 15.3 µg  permeation from 0.5092 mg NMN per µND array (24h). Additionally, significant NAD+ levels in ex-vivo donor skin was seen due to skin treatment with NMN- µND array (0.3707 & 0.5092 mg NMN load/array, n=4) in the stratum granulosum and spinosum of the epidermal layers. Our study demonstrated successful delivery of NAD+ precursor molecule through dissolvable µNDs as an alternative to oral delivery

  1. Okabe, K., et al., Implications of altered NAD metabolism in metabolic disorders. Journal of biomedical science, 2019. 26(1): p. 34.
  2. Rajman, L., K. Chwalek, and D.A. Sinclair, Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metabolism, 2018. 27(3): p. 529-547.