Bioinspired apixaban nanosuspension-loaded polymeric microneedle arrays for non-invasive transdermal delivery: a...

Apixaban (APX), an anticoagulant drug with indications in managing strokes, systemic embolism and deep vein thrombosis, has been of great interest since COVID-19 pandemic. We investigated, for the first time, the non-invasive transdermal delivery of APX nanosuspension (NS)-loaded microneedle (MN) array patches using sodium alginate (SA) and pectin polymers, to enhance its bioavailability and improve patient compliance. APX-SA-NS and APX-pectin-NS were formulated and screened using emulsification solvent evaporation technique, acquiring particle sizes of 405.25 ± 8.41 and 443.3 ± 27.31 nm, respectively, then incorporated into MN arrays, and subjected to morphological examination, texture analyses, ex vivo skin penetration/permeation and in vivo pharmacokinetic studies. APX-SA-MNs and APX-pectin-MNs visualized by various imaging techniques had fitting mechanical strength with effective skin piercing/insertion properties, reaching depths of 504 and 630 μm, respectively, adequate for transdermal drug delivery. Ex vivo experiments and in vivo pharmacokinetics revealed the superiority of SA-MNs over pectin-MNs in skin permeation with respective area under the curve values reaching 7500.03 ± 1326.31 and 2181.92 ± 777.07 ng/ml*h, compared to 4120.48 ± 148.48 ng/ml*h for the oral marketed tablet Apixatrack®. SA-MNs also exhibited exceptional prolonged mean residence times and relative bioavailability. Histopathology indicated the skin-friendly impact of SA-MNs patches, whereas, pectin-MNs showed signs of inflammation, endorsing SA superiority for APX delivery via ensuring a lower dosing frequency, enhanced drug efficacy, and increased patient compliance.