Spatiotemporal fate of nanocarriers-embedded dissolving microneedles: the impact of needle dissolving rate

ABSTRACT

Objective

Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems.

Methods

Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties. Sodium hyaluronate acid (HA) and chitosan (CS), with different aqueous dissolving rates, were chosen as model tip materials. The effects of needle dissolving rate on the in vivo fate of NC-loaded DMNs was investigated by tracking the distribution of fluorescence signals after transdermal exposure.

Results

P4 SLNs achieved a deeper diffusion depth of 180 μm in DMN-HA with a faster dissolution rate, while the diffusion depth in DMN-CS with a slower dissolution rate was lower (140 μm). The in vivo experiments demonstrated that P4 SLNs had a T_1/2 value of 12.14 h in DMN-HA, whilst a longer retention time was found in DMN-CS, with a T_1/2 of 13.12 h.

Conclusions

This study confirmed that the in vivo diffusion rate of NC-loaded DMNs was determined by the dissolving rate of DMNs materials and provided valuable guidance for the design and development of NC-loaded DMNs in the future.

KEYWORDS:

• Dissolving microneedles
• solid lipid nanoparticles
• aggregation-caused quenching
• in vivo fate
• dissolving rate
• diffusion rate

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception and design: J Cong, Z Zheng, Z Huang, G Quan; Analysis and interpretation of data and drafting of the paper: J Cong, Z Zheng; Revising of the paper, final approval of the version to be published, agree to be accountable for all aspects of the work: All authors.

Acknowledgments

Authors would like to thank Wei Wu’s group at Fudan University for the donation of P4 probes.

Data availability statement

Data is available on request.

Additional information

Funding

This study was funded by the National Natural Science Foundation of China [No. 82173747, China], the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province [No. 2021TQ060944, China], and the Guangdong Basic and Applied Basic Research Foundation [No. 2024A1515011236].