Abstract
Biodegradable polymer microneedles (MNs) are recognized as non-toxic, safe and stable systems for advanced drug delivery and cutaneous treatments, allowing a direct intradermal delivery and in some cases a controlled release. Most of the microneedles found in the literature are fabricated by micromolding, which is a multistep thus typically costly process. Due to industrial needs, mold-free methods represent a very intriguing approach in microneedle fabrication. Electro-drawing (ED) has been recently proposed as an alternative fast, mild temperature and one-step strategy to the mold-based techniques for the fabrication of poly(lactic-co-glycolic acid) (PLGA) biodegradable MNs. In this work, taking advantage of the flexibility of the ED technology, we engineered microneedle inner microstructure by acting on the water-in-oil (W/O) precursor emulsion formulation to tune drug release profile. Particularly, to promote a faster release of the active pharmaceutical ingredient, we substituted part of PLGA with poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP/VA), as compared to the PLGA alone in the matrix material. Moreover, we introduced lecithin and maltose as emulsion stabilizers. Microneedle inner structural analysis as well as collagenase entrapment efficiency, release and activity of different emulsion formulations were compared to reach an interconnected porosity MN structure, aimed at providing an efficient protein release profile. Furthermore, MN mechanical properties were examined as well as its ability to pierce the stratum corneum on a pig skin model, while the drug diffusion from the MN body was monitored in an in vitro collagen-based dermal model at selected time points.
Highlights
Biocompatible microneedles (MNs) have recently gained great attention, being recognized as a pain-free and successful administration route, alternative to injection thatElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Most of the MN fabrication methodologies reported in literature, are based on micromolding (Jamaledin et al 2020; Li et al 2019; Nejad et al 2018)
Electro-drawing is a mask-less and mold-less 3D lithography process by which microneedles are fabricated under the action of electro-hydrodynamic pressure induced by a pyroelectric effect (Ruggiero et al 2018; Vecchione et al 2014), Fig. 1b and c
Microneedle porosity represents a big issue in drug delivery applications since it is related to the amount of drug that can be loaded inside the polymeric matrix, and as a consequence, successively released in the body
Summary
Mold-free microneedle fabrication techniques, based on drawing lithography (Lee and Jung 2012), droplet-born air blowing (DAB) (Kim et al 2013a, b), cyclic contact and drying process on pillars (CCDP process) (Kim et al 2015), have been proposed as potential solutions to several of the technological limitations affecting micromolding. These methods, despite being free of master fabrication processes or replica molding, are affected by limits arising from high process temperatures or features of reproducibility typically lower than the mold-based processes
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