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Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP
Abbie Omolu1, Maryse Bailly2, Richard M Day1
1a Applied Biomedical Engineering Group, Division of Medicine , University College London , London , UK.
Abstract:
Many chronic wounds exhibit high matrix metalloproteinase (MMP) activity that impedes the normal wound healing process. Intradermal delivery (IDD) of sub-antimicrobial concentrations of doxycycline, as an MMP inhibitor, could target early stages of chronic wound development and inhibit further wound progression. To deliver doxycycline intradermally, the skin barrier must be disrupted. Microneedle rollers offer a minimally invasive technique to penetrate the skin by creating multiple microchannels that act as temporary conduits for drugs to diffuse through. In this study, an innovative and facile approach for delivery of doxycycline across Strat-MTM membrane was investigated using microneedle rollers. The quantity and rate of doxycycline diffusing through the micropores directly correlated with increasing microneedle lengths (250, 500 and 750 microm). Treatment of Strat-MTM with microneedle rollers resulted in a reduction in fibroblast-mediated collagen gel contraction and MMP activity compared with untreated Strat-MTM. Our results show that treatment of an epidermal mimetic with microneedle rollers provides sufficient permeabilization for doxycycline diffusion and inhibition of MMP activity. We conclude that microneedle rollers are a promising, clinically ready tool suitable for delivery of doxycycline intradermally to treat chronic wounds.
Insights
Microneedle rollers effectively deliver doxycycline intradermally, inhibiting matrix metalloproteinase (MMP) activity. This minimally invasive method shows promise for treating chronic wounds by improving drug diffusion and reducing MMP-driven tissue damage.
Area of Science:
- Biomedical Engineering
- Dermatology
- Pharmacology
Background:
- Chronic wounds often show elevated matrix metalloproteinase (MMP) activity, hindering healing.
- Sub-antimicrobial doxycycline concentrations can inhibit MMPs, potentially aiding wound healing.
- Intradermal drug delivery requires overcoming the skin barrier.
Purpose of the Study:
- To investigate microneedle rollers for intradermal delivery of doxycycline.
- To assess doxycycline diffusion and MMP inhibition using an epidermal model.
- To evaluate microneedle rollers as a tool for chronic wound treatment.
Main Methods:
- Microneedle rollers of varying lengths (250, 500, 750 microm) were used to create microchannels in a Strat-M™ membrane.
- Doxycycline diffusion through the membrane was quantified.
- The effect of microneedle treatment on fibroblast-mediated collagen gel contraction and MMP activity was assessed.
Main Results:
- Doxycycline diffusion rate and quantity increased with longer microneedle lengths.
- Microneedle roller treatment reduced fibroblast-mediated collagen gel contraction.
- Significant reduction in MMP activity was observed in treated Strat-M™ samples.
Conclusions:
- Microneedle rollers facilitate doxycycline diffusion across the skin barrier.
- This approach effectively inhibits MMP activity in an epidermal model.
- Microneedle rollers represent a promising, clinically applicable tool for intradermal doxycycline delivery in chronic wound management.
