Abstract

Polymeric microneedles are introduced as a promising platform for minimally invasive drug delivery and molecular transport control. In the present study, hollow dissolving nanocomposite microneedles based on a mixture of high- and low-molecular-weight hyaluronic acid (HA) in a 40:60 ratio, including zinc oxide nanoparticles (ZnO NPs), have been created and evaluated as hydrated polymer transport matrices. Surface modification of ZnO nanoparticles using citric acid was proposed to improve dispersion by reducing agglomeration of nanoparticles in the polymer matrix. ZnO nanoparticles in concentrations ranging from 1 to 10% (w/w) were used to study the effects of the loading level of nanoparticles on the structure, mechanical response, and controlled diffusion behavior of hydrated polymer matrices. The created nanocomposites exhibited clear hollow structures with tip radius of 18–23 μm, height of 1500 μm, and aspect ratio of 5.7. Nanoscale surface organization and particle dispersion in the polymer matrix were studied by scanning electron microscope (SEM) and atomic force microscope (AFM). Low nanoparticle concentrations were favorable for maintaining high matrix homogeneity, while high concentrations resulted in increased surface roughness and nanoparticle agglomeration. Mechanical compression testing confirmed that hydrated HA/ZnO microneedles were characterized by elastic bending behavior until fracture. Diffusion experiments performed in Franz diffusion cells showed that nanoparticle concentration significantly impacted the cumulative transport and flux of molecules through the hydrated microneedle matrix. Formulations with 5% and 7% ZnO nanoparticles were characterized by a prolonged diffusion behavior attributed to ZnO-induced tortuous transport channels in the polymer matrix. In contrast, formulations with 10% ZnO nanoparticles exhibited accelerated heterogeneous transport due to ZnO-induced changes in structure and morphology. The experimental diffusion data correlated well with the Higuchi kinetic model, and anomalous transport was detected using the Korsmeyer–Peppas model, which indicated a synergistic effect of diffusion and polymer relaxation on molecular transport. As compared to coating and tip-loaded microneedle designs, the obtained HA/ZnO nanocomposite microneedles offered a simple approach for embedding Ciprofloxacin in the hydrated polymer matrix. This was achieved due to the direct creation of microneedles containing dissolved particles.

IPC Classification

Keywords