Cyanocobalamin-loaded dissolving microneedles for enhanced transdermal delivery: development, characterization, and pharmacokinetic evaluation

This study demonstrates cyanocobalamin-loaded dissolving microneedles (CNBL-MNs) as a minimally invasive transdermal solution for managing cyanocobalamin (CNBL) deficiency, offering an alternative to intramuscular injections and oral supplements. The CNBL-MNs were developed using biodegradable, water-soluble polymers such as polyvinylpyrrolidone K25, Dextran K40, and chitosan to ensure controlled and gradual release of the CNBL. The formulation’s stability and integrity were assessed through FTIR and XRD analyses. SEM imaging revealed well-formed microneedles with a height of 800 μm, a 200 μm base diameter, and a 500 μm pitch. EDS confirmed the successful incorporation of CNBL in the microneedle array. The Parafilm^® membrane insertion test revealed that the microneedles had strong mechanical properties and achieved 100% penetration efficiency. The microneedle array also demonstrated excellent (P > 0.05) flexibility and structural stability. Ex-vivo release studies showed that 88.51% of the CNBL was released over 48 h, following a first-order kinetic model. The n value of 0.51 for Korsmeyer-Peppas model indicate an anomalous transport mechanism, suggesting a combination of diffusion and erosion. The in-vivo pharmacokinetic evaluation in Wistar rats demonstrates that CNBL-MNs-2 exhibited a larger area under the curve (AUC₀–t) (61.57 ± 4.23 ng·h/mL) than the IP injection (37.04 ± 5.83 ng·h/mL), indicating significant (p > 0.05) increase in systemic availability and sustained release. The Cmax of CNBL-MNs-2 (6.10 ± 0.533 ng/mL) was comparable to that of the IP injection (6.20 ± 1.5 ng/mL), confirming efficient systemic absorption via the microneedle system. Additionally, Tmax was significantly (p > 0.05) prolonged with CNBL-MNs-2 (8 h) compared to the IP injection (2 h), suggesting a slower, more controlled CNBL release.