Transdermal delivery of vitamin K using dissolving microneedles for the prevention of vitamin K deficiency bleeding

Aaron R.J Hutton,Helen L Quinn,Paul J Mccague,Courtney Jarrahian,Annie Rein-Weston,Patricia S Coffey,Emily Gerth-Guyette,Darin Zehrung,Eneko Larrañeta,Ryan F Donnelly

doi:10.1016/j.ijpharm.2018.02.031

Abstract

Vitamin K deficiency within neonates can result in vitamin K deficiency bleeding. Ensuring that newborns receive vitamin K is particularly critical in places where access to health care and blood products and transfusions is limited. The World Health Organization recommends that newborns receive a 1 mg intramuscular injection of vitamin K at birth. Evidence from multiple surveillance studies shows that the introduction of vitamin K prophylaxis reduces the incidence of vitamin K deficiency bleeding. Despite these recommendations, coverage of vitamin K prophylactic treatment in low-resource settings is limited.An intramuscular injection is the most common method of vitamin K administration in neonates. In low- and middle-income countries, needle sharing may occur, which may result in the spread of bloodborne diseases. The objective of our study was to investigate the manufacture of microneedles for the delivery of vitamin K. Following microneedle fabrication, we performed insertion studies to assess the microneedle’s mechanical properties. Results indicate that vitamin K in a microneedle array was successfully delivered in vitro across neonatal porcine skin with 1.80 ± 0.08 mg delivered over 24 h. Therefore, this initial study shows that microneedles do have the potential to prevent vitamin K deficiency bleeding. Future work will assess delivery of vitamin K in microneedle array in vivo.

Highlights

Vitamin K, a fat-soluble vitamin, functions as a cofactor for gammacarboxylase enzymes within the liver (Ozdemir et al, 2012)
Evidence from multiple surveillance studies shows that the introduction of vitamin K prophylaxis reduces the incidence of vitamin K deficiency bleeding
A dissolving MN formulation based on 20% w/w Gantrez® S-97, 5% w/w Tween® 80, and 2% w/w vitamin K produced fully formed, sharp needles with a strong baseplate

Summary

Introduction

Vitamin K, a fat-soluble vitamin, functions as a cofactor for gammacarboxylase enzymes within the liver (Ozdemir et al, 2012) This role enables posttranslational conversion of inactive hepatic precursors II, VII, IX, and X into active clotting factors through gamma-carboxylation of glutamic acid residues (Shearer, 1995; Smith et al, 2015). VKDB can present as an intracranial haemorrhage during the first 24 h of birth This particular form is most common in newborns whose mothers have been prescribed antiepileptics, anticoagulants, or other medicines that interact and prevent the normal functioning of vitamin K (Shearer, 2009). In contrast to early VKDB, the classic form of this condition is largely regarded as idiopathic with the gastrointestinal tract, umbilical region, and skin, which are defined as common bleeding sites.

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Conclusion