# Single Polysaccharide Dissolvable Microneedles for Painless Local Anesthesia: Fabrication, Characterization, and In Vitro Neuronal Imaging

**Authors:** João M. S. P. Leite, Ana C. Q. Silva, Ana Jesus, Bruna C. da Cruz, Sandra I. Vieira, Patrícia Dias-Pereira, Paulo C. Costa, Isabel F. Almeida, Inês Correia-Sá, Armando J. D. Silvestre, Bruno M. Neves, Carla Vilela, Carmen S. R. Freire

PMC · DOI: 10.1021/acsbiomaterials.5c00968 · ACS Biomaterials Science & Engineering · 2025-08-01

## TL;DR

Researchers developed dissolvable microneedles made of a single polysaccharide to deliver lidocaine painlessly through the skin, showing they work well in lab tests.

## Contribution

A single-component polysaccharide-based microneedle system for transdermal lidocaine delivery with rapid onset and high compatibility.

## Key findings

- Pullulan microneedles sustained up to 1.5 N force and successfully pierced human abdominal skin to reach the dermis.
- The microneedles dissolved within 10 minutes in skin models, retaining 26-32% lidocaine for effective local anesthesia.
- Lidocaine released from microneedles showed comparable activity to pure lidocaine on sensory neurons in fluorescence tests.

## Abstract

In recent years, microneedles (MNs)
have shown high potential
as
drug delivery devices capable of administering different drugs in
a simple, fast, and minimally invasive manner. Their ability to pierce
the stratum corneum barrier heavily outweighs the inconveniences posed
by conventional administration methods such as hypodermal injections,
creams, or ointments. In this work, high-performance, single-component
polysaccharide-based microneedles, viz. pullulan
MNs, were produced by micromolding, aimed for transdermal delivery
of lidocaine. These dissolvable MNs were able to sustain forces up
to 1.5 N per needle without breakage. Their ability to overcome the
stratum corneum was validated using excised human abdominal skin,
with the MNs successfully reaching the dermis. The MN tips completely
dissolved after 10 min in an agarose gel skin model and porcine ear
skin, with 26 and 32% of lidocaine being retained in the patch after
10 min of insertion in the agarose gel and porcine skin, respectively.
Cytocompatibility against multiple cell lines (HaCaT, 3T3, and RAW
264.7) was demonstrated by the resazurin metabolic assay, with over
80% cell viability in all cases. Time-lapse fluorescence microscopy
confirmed that the activity of the MN-released lidocaine on sensory
neurons was comparable to that of a pure lidocaine solution at a similar
concentration. In sum, given its low onset time (<10 min), swift
dissolution, and effective drug release, this pullulan-based system
constitutes a simple, safe, and efficient delivery device, contrasting
conventional methods of local anesthetic administration.

## Linked entities

- **Chemicals:** lidocaine (PubChem CID 3676)

## Full-text entities

- **Chemicals:** agarose (MESH:D012685), resazurin (MESH:C005843), lidocaine (MESH:D008012), Polysaccharide (MESH:D011134)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), 3T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12818717/full.md

## References

84 references — full list in the complete paper: https://tomesphere.com/paper/PMC12818717/full.md

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Source: https://tomesphere.com/paper/PMC12818717