Photo-crosslinkable polyester microneedles as sustained drug release systems toward hypertrophic scar treatment

Abstract

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly(ε-caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization (¹H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

Graphical abstract

HIGHLIGHTS

• AUP-PCL MN arrays provide long-term transdermal drug delivery of hydrocortisone

• AUP-PCL-based MN arrays provide superior drug release profiles compared to PCL MNs

• Effective skin penetration AUP-PCL-based MNs on skin was achieved

Keywords:

• Microneedles
• polyester
• cortisone
• hypertrophic scarring
• controlled drug release
• intradermal drug delivery

Acknowledgements

The authors would like to thank Evelien Vermoesen for the help with regard to the AUP-PCL synthesis. The authors would additionally like to thank Irem Kaya for preparing the histological slices and for providing technical support for the histological evaluation.

Disclosure of interest

Sandra Van Vlierberghe is a co-founder of the companies BIO INX BV and 4Tissue BV, but the author declares to have no known financial interest that could have appeared to influence the work reported in this paper. The other authors declare to have no competing financial or commercial interest or personal relationship that could have appeared to influence the work reported in this manuscript.

Ethical approval

This study did not include treatment of human participants. The collection of and testing on ex vivo human skin was approved by the Ethical Committee of the Ghent University Hospital on the 28th of December 2021 and received the registration code BC-11330. Patients were asked to give oral and written informed consent for skin sample collection.

Author contributions

Anna Szabó was responsible for conceptualization, the development of the MN arrays with regard to material selection, development and characterization, MN fabrication and characterization, along with Sam Samey, and preparation of the manuscript.

Ignace De Decker was responsible for conceptualization, the ex vivo evaluation of the developed MN arrays, along with Sam Samey, and preparation of the manuscript.

Karel E.Y. Claes, Phillip Blondeel, Stan Monstrey, Jo Van Dorpe and Sandra Van Vlierberghe were responsible for conceptualization, along with evaluating the experimental plan, development of the MN arrays and contributed to the preparation of the manuscript.

Supporting Information

Supporting Information is available from the Online Library or from the authors.

Data availability statement

The data gained during the preparation of the manuscript are available upon request from the corresponding author, Sandra Van Vlierberghe.

Additional information

Funding

This research has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 828835.