The spatial-dimensional and temporal-dimensional fate of nanocarrier-loaded dissolving microneedles with different lengths of needles

Highlights

• P4 probes with aggregation caused quenching property enabled the signal discrimination of integrated nanocarriers (NC) from disintegrated NC.

• Clarify the effect of the height of dissolving microneedles (DMNs) on in vivo fate of NC loaded in DMNs from spatial and temporal perspectives.

• Facilitate the clinical translation of NC-incorporated DMNs.

Abstract

Dissolving microneedles (DMNs) hold great popularity because of their precise drug delivery and administration portability. DMNs with different lengths could reach different depths of punctures that consequently resulted in different diffusive effects. Therefore, to clarify the effect of the length of the needles on in vivo fate of DMNs is of great significance. In this study, solid lipid nanoparticles (SLNs) were chosen as the model NC loaded in DMNs. To unambiguously determine the biological fate of the DMNs, P4 probe with aggregation caused quenching property was encapsulated in SLNs to enable the visualization of the process of the disintegration of SLNs. P4-encapsulated SLNs were loaded into DMNs with the lengths of 1200 μm, 800 μm, and 400 μm (named as DMN-1200, DMN-800, and DMN-400). By tracking the fluorescence signal distribution after skin piercing, the influence of the lengths of the needles on DMNs to the in vivo fate of the intact SLNs was explored. In the spatial dimension, intact NC loaded DMNs showed a length-dependent diffusion depth. In the temporal dimension, the diffusion rates of DMN-1200, DMN-800, and DMN-400 were similar within 24 h after insertion. It was inferred that DMNs with shorter needles would be ideal for the diseases on the superficial layer of the skin, while the ones with longer needles could be utilized in the treatment of diseases in deeper dermal and subcutaneous layers. The results of the study can act as a valuable guidance for future design and development of NC-loaded DMNs.