Transdermal delivery of vitamin B12 (Vit-B12) is challenging due to its high hydrophilicity and molecular weight that limit permeation through the skin. Polymeric microneedles (MNs) have been demonstrated to facilitate enhanced transdermal delivery of various drugs with different properties, by piercing the outermost layer of the skin barrier in a minimally-invasive manner. Although sodium alginate (SA) has been widely investigated and used for pharmaceutical and biomedical applications, MNs made of pure SA, exhibit poor mechanical properties. Therefore, this study investigates the effect of incorporating different excipients into SA MNs, to enhance their insertion ability and mechanical performance, by a modified vacuum deposition micromolding method. Among these, poly(vinylpyrrolidone) (PVP) and polyethylene glycol (PEG)-containing SA MNs at a ratio of 1:8 show improved mechanical strength with minimal height reduction (< 10%) at all tested forces, and higher insertion capabilities into a skin-simulant parafilm model (> 65% in the second layer), compared to control SA MNs. Consequently, Vit-B12 was successfully loaded and concentrated into the MN shafts of the lead formulations, by the addition of hydroxypropyl cellulose to the baseplate. Vit-B12 MNs were characterized by means of fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) measurements, drug loading and dissolution kinetics. The MNs exhibited adequate mechanical properties and a complete drug release within 30 min, while a considerable fraction was released after few minutes. The present study shows promising findings regarding the potential use of SA in the preparation of dissolving MNs with enhanced mechanical performance for transdermal delivery of Vit-B12. However, further preclinical investigations are necessary to comprehensively evaluate their therapeutic efficacy. Additionally, this work suggests that alginate-based blend MNs may have a potential application in the delivery of other hydrophilic and large compounds for improved therapeutic outcomes.
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