Pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment

• Dissolvable pullulan microneedles were successfully prepared by solvent casting. • Pullulan-insulin microneedles successfully penetrate through the skin. • Storage at 4, 20 and 40 °C maintained the secondary structure of insulin. • Pullulan microneedles deliver 87% of insulin, 120 min after insertion. • Pullulan-insulin microneedles are non-cytotoxic towards human keratinocyte cells. The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (T dmax = 294 °C) and mechanical properties (>0.15 N needle −1 ), penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro , the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. These findings suggest that PL MNs have potential to deliver insulin transdermally, thus avoiding its subcutaneous administration.