Preparation and characterization of 3D printed PLA microneedle arrays for prolonged transdermal drug delivery of estradiol valerate.

Biodegradable polymeric microneedle arrays (BPMNAs) could be explored as potential devices for transdermal drug delivery, which can provide a painless and safe drug delivery method. BPMNAs could also provide high drug-loading capacity and prolonged drug delivery once integrated with a drug reservoir. However, the fabrication of MNAs with a drug reservoir is expensive and requires complicated procedures. The present study was conducted to describe the preparation of a reservoir-based BPMNA containing estradiol valerate using polylactic acid (PLA) with the combination of FDM 3D printing and injection volume filling techniques. The tip size of the 3D printed needles decreased to 173 μm utilizing a chemical etching process. The content of estradiol valerate loaded in the 3D printed PLA MNAs was 29.79 ± 0.03 mg, and the release was in a prolonged manner for up to 7 days. The results of mechanical tests revealed that the force needed for the 3D printed PLA MNAs fracture (900 N) was significantly higher than that needed for their skin penetration (4 N). The successful penetration of 3D printed PLA MNAs through the stratum corneum was confirmed via penetration test, methylene blue staining, and histological examination. The results showed that 3D printed PLA MNAs can penetrate into the skin without reaching to the dermal nerves and puncture of blood vessels. In conclusion, in the current study, we explored the practicability of the preparation of drug loaded reservoir-based BPMNAs using the combination of FDM 3D printing and injection volume filling techniques for painless and prolonged transdermal drug delivery.