Hydrogel Microneedles with Programmed Mesophase Transitions for Controlled Drug Delivery

Hala Dawud, Nicole Edelstein-Pardo, Keerthana Mulamukkil, Roey J. Amir*, Aiman Abu Ammar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Microneedle-based drug delivery offers an attractive and minimally invasive administration route to deliver therapeutic agents through the skin by bypassing the stratum corneum, the main skin barrier. Recently, hydrogel-based microneedles have gained prominence for their exceptional ability to precisely control the release of their drug cargo. In this study, we investigated the feasibility of fabricating microneedles from triblock amphiphiles with linear poly(ethylene glycol) (PEG) as the hydrophilic middle block and two dendritic side-blocks with enzyme-cleavable hydrophobic end-groups. Due to the poor formation and brittleness of microneedles made from the neat amphiphile, we added a sodium alginate base layer and tested different polymeric excipients to enhance the mechanical strength of the microneedles. Following optimization, microneedles based on triblock amphiphiles were successfully fabricated and exhibited favorable insertion efficiency and low height reduction percentage when tested in Parafilm as a skin-simulant model. When tested against static forces ranging from 50 to 1000 g (4.9-98 mN/needle), the microneedles showed adequate mechanical strength with no fractures or broken segments. In buffer solution, the solid microneedles swelled into a hydrogel within about 30 s, followed by their rapid disintegration into small hydrogel particles. These hydrogel particles could undergo slow enzymatic degradation to soluble polymers. In vitro release study of dexamethasone (DEX), as a steroid model drug, showed first-order drug release, with 90% released within 6 days. Eventually, DEX-loaded MNs were subjected to an insertion test using chicken skin and showed full penetration. This study demonstrates the feasibility of programming hydrogel-forming microneedles to undergo several mesophase transitions and their potential application as a delivery system for self-administration, increased patient compliance, improved efficacy, and sustained drug release.

Original languageEnglish
Pages (from-to)1682-1693
Number of pages12
JournalACS Applied Bio Materials
Volume7
Issue number3
DOIs
StatePublished - 18 Mar 2024

Funding

FundersFunder number
Israeli Ministry of Innovation, Science and Technology
Israel Science Foundation413/22
Tel Aviv University
Ministry of Science and Technology, Israel

    Keywords

    • PEG
    • biodegradable
    • controlled release
    • enzyme-responsive polymers
    • hydrogels
    • in situ forming hydrogel
    • microneedles
    • programmable mesophase transitions
    • steroids

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