Protease-Responsive Hydrogel Microparticles for Intradermal Drug Delivery

Heidi K. Noddeland, Marianne Lind, Karsten Petersson, Frank Caruso, Martin Malmsten, Andrea Heinz

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Protease-responsive multi-arm polyethylene glycol-based microparticles with biscysteine peptide crosslinkers (CGPGG↓LAGGC) were obtained for intradermal drug delivery through inverse suspension photopolymerization. The average size of the spherical hydrated microparticles was ∼40 μm after crosslinking, making them attractive as a skin depot and suitable for intradermal injections, as they are readily dispensable through 27G needles. The effects of exposure to matrix metalloproteinase 9 (MMP-9) on the microparticles were evaluated by scanning electron microscopy and atomic force microscopy, demonstrating partial network destruction and decrease in elastic moduli. Given the recurring course of many skin diseases, the microparticles were exposed to MMP-9 in a flare-up mimicking fashion (multiple-time exposure), showing a significant increase in release of tofacitinib citrate (TC) from the MMP-responsive microparticles, which was not seen for the non-responsive microparticles (polyethylene glycol dithiol crosslinker). It was found that the degree of multi-arm complexity of the polyethylene glycol building blocks can be utilized to tune not only the release profile of TC but also the elastic moduli of the hydrogel microparticles, with Young’s moduli ranging from 14 to 140 kPa going from 4-arm to 8-arm MMP-responsive microparticles. Finally, cytotoxicity studies conducted with skin fibroblasts showed no reduction in metabolic activity after 24 h exposure to the microparticles. Overall, these findings demonstrate that protease-responsive microparticles exhibit the properties of interest for intradermal drug delivery.

Originalspråkengelska
Sidor (från-till)3203-3214
Antal sidor12
TidskriftBiomacromolecules
Volym24
Nummer7
DOI
StatusPublished - 2023 juli 10

Ämnesklassifikation (UKÄ)

  • Farmaceutisk vetenskap
  • Kemi

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