Bioinspired labrum-shaped stereolithography (SLA) assisted 3D printed hollow microneedles (HMNs) for effectual delivery of ceftriaxone sodium

Abstract

Microneedles (MNs), a microsystem having needle height in micrometers, have gained significant attention due to their minimum invasiveness, painless, and easy-to-administer nature. Here, we introduce a hollow microneedle (HMNs) array with bio-inspired labrum tip for low insertion force and desired mechanical strength, fabricated using vat-photopolymerization mediated stereolithography (SLA) assisted 3D printing technology utilizing biocompatible photo-crosslinkable and curable resin as feedstock. Fabricated HMNs was used for the effective transdermal delivery of a broad-spectrum antibiotics i.e., ceftriaxone sodium (CEF) with a high molecular weight of 554.58 g mol−1, possessing gastro-intestinal (GI) instability and low oral bioavailability (BA). The bio-inspired labrum tip structure of the fabricated HMNs was evaluated by digital microscopy and scanning electron microscopy (SEM) to ensure the printed prototype's superiority in terms of dimensions and array uniformity. The HMN microchannels were then characterized by X-ray microcomputer tomography (µCT) to ascertain the quality of internal channels and ensure even distribution of drug solution. Further, HMNs was also characterized for mechanical and penetration analysis. Suggesting a low force of 1.54 N was required for its effective penetration with a sufficient fracture force of around 171.82 N. The ex vivo skin permeation profile of CEF from the HMNs revealed 100 ± 0.80 % CEF permeation through porcine skin within 18 hr. Finally, a pre-clinical efficacy assessment of CEF-reservoir HMNs was performed in an experimental animal model, revealing efficient penetrability and desired BA of CEF. Overall results demonstrated the active transdermal drug delivery potential of these fabricated bio-inspired HMNs as a unique device for customized and personalized treatment.