Single Polysaccharide Dissolvable Microneedles for Painless Local Anesthesia: Fabrication, Characterization, and In Vitro Neuronal Imaging.

Abstract

In recent years, microneedles (MNs) have shown high potential as drug delivery devices capable of administering different drugs in a simple, fast, and minimally invasive manner. Their ability to pierce the stratum corneum barrier heavily outweighs the inconveniences posed by conventional administration methods such as hypodermal injections, creams, or ointments. In this work, high-performance, single-component polysaccharide-based microneedles, viz. pullulan MNs, were produced by micromolding, aimed for transdermal delivery of lidocaine. These dissolvable MNs were able to sustain forces up to 1.5 N per needle without breakage. Their ability to overcome the stratum corneum was validated using excised human abdominal skin, with the MNs successfully reaching the dermis. The MN tips completely dissolved after 10 min in an agarose gel skin model and porcine ear skin, with 26 and 32% of lidocaine being retained in the patch after 10 min of insertion in the agarose gel and porcine skin, respectively. Cytocompatibility against multiple cell lines (HaCaT, 3T3, and RAW 264.7) was demonstrated by the resazurin metabolic assay, with over 80% cell viability in all cases. Time-lapse fluorescence microscopy confirmed that the activity of the MN-released lidocaine on sensory neurons was comparable to that of a pure lidocaine solution at a similar concentration. In sum, given its low onset time (<10 min), swift dissolution, and effective drug release, this pullulan-based system constitutes a simple, safe, and efficient delivery device, contrasting conventional methods of local anesthetic administration.