Rapid dissolving microneedles arrays for intradermal administration of Hyaluronic Acid from 3D printing and micromolding.

Abstract

Microneedles (MA) are an emerging technology consisting of multiple microscopic projections smaller than 1000 μm in height, formed by biocompatible polymers placed on a single side of a support base or patch. It is characterized as a minimally invasive technique for various procedures such as therapeutics, disease monitoring and diagnostics. After application to the skin, the MAs penetrate the epidermal layer and, according to their length, act on the different layers of the skin. In this way, these systems allow the delivery possibilities to a wider range of drugs and biotherapeutic macromolecules.

Five microneedle designs with different geometries and dimensional relationships were developed. They were printed using LCD 3D printing technology and the dimensional input and output parameters were compared in order to assess their resolution and fidelity. Subsequently, a design was selected based on these quality parameters and MA matrices formed by Hyaluronic Acid (HA) 10% w/v with the incorporation of glycerin in different proportions (1, 2 and 3 % w/v) in the support base were prepared. These systems were obtained by "ring" assisted micromolding from matrices designed and fabricated by FDM 3D printing. The influence of the base/support materialization on the resistance to deformation of the MAs was evaluated, with the aim of obtaining greater adaptability and manipulation of the patch on the skin. The systems were characterized mechanically through compression tests (10,20 and 32 N), tensile tests and morphologically from images taken before and after the aforementioned tests through an optical microscope and analyzed with ImageJ software. Finally, to evaluate the penetrability in skin, ex-vivo insertion tests were performed in rat skin, as well as the dissolution rate of the same, in a medium that mimics physiological conditions. MA arrays composed of 100 microprojections of heights between 300 and 700 μm with distances of 1 mm between them were obtained. In compression and tensile tests it was observed that by increasing the concentration of glycerin the system decreases its modulus of elasticity, which causes a lower deformation at low stresses, with respect to its initial dimensions. In correlation with these results, the ex-vivo tests showed that the penetrability power of the system decreases as the glycerin concentration in its base increases, observing at 3% w/v that the effectiveness was 17% while the s/glycerin matrices presented a greater effectiveness in penetration of 57%. Finally, in in-vitro dissolution tests with s/glycerin backing, it was corroborated that HA MAs have an average speed of 6 min, achieving rapid action in the desired area.