Advancement in Emergency Opioid Overdose Treatment: Iontophoresis-Enabled Microneedle Skin Patch Delivering Naloxone
Location
D.P. Culp Center Ballroom
Start Date
4-5-2024 9:00 AM
End Date
4-5-2024 11:30 AM
Poster Number
113
Name of Project's Faculty Sponsor
Ashana Puri
Faculty Sponsor's Department
Pharmaceutical Sciences
Competition Type
Competitive
Type
Poster Presentation
Presentation Category
Health
Abstract or Artist's Statement
The administration of naloxone for reversing opioid overdose is predominantly restricted to invasive injectables, due to its susceptibility to significant hepatic clearance when given traditionally. However, these delivery routes often entail discomfort and necessitate frequent injections to stabilize patients owing to NAL's short half-life. Introducing alternative delivery systems could prove advantageous, particularly if they offer a balance between sustained release characteristics and rapid onset. Intranasal delivery has been considered, but this has pitfalls including limited use due to damaged nasal mucosa, unpredictable responses, also sustained delivery is not feasible with this. Consequently, our study aims to develop a clinically feasible system of NAL offering clinically relevant attributes. In this study, we examined the transdermal delivery of naloxone using polymeric rapidly dissolving microneedles (MNs). We investigated how MN geometrical parameters affect NAL delivery and made pharmacokinetic predictions to anticipate in vivo delivery based on in vitro permeation profiles. Additionally, our investigation delved into the potential of iontophoretically driving ionized drug content within MN patches to augment the cumulative permeation of NAL. We refined the iontophoresis parameters by examining how changes in the strength of citrate phosphate buffer impact the drug release profile. Additionally, we investigated the potential benefits of integrating iontophoresis with higher drug loading to improve the patch's effectiveness. We explored the influence of current density, pH changes and competing ions on delivery profile from the iontophoresis coupled microneedle patches. Our observations showed a notable decrease in the lag time for delivering NAL to approximately 5-15 min using MN patches, compared to the typical 75 min with passive transdermal delivery. Increasing the length and density of MNs had a significant impact on the amount permeated and flux over a 24-hour period (p<0.05). Mathematical modeling of in-vitro release from the most effective patch highlighted the importance of needle base diameter and needle count in enhancing the systemic pharmacokinetics of NAL from the MN patches. This approach allowed us to predict an optimized patch design capable of replicating the clinical pharmacokinetics of NAL achieved with commercial devices. With the coupling of iontophoresis to the MN patches, the average cumulative permeation observed was 1331.44 ± 397.57 µg/cm2 within 1h while this was 103.00 ± 15.18 µg/cm2 with a basic patch. Similarly, the average flux over 1h was 619.09 ± 111.95 µg/cm2 with the iontophoresis coupled MN patch a remarkable increase over 102.98 ± 16.02 µg/cm2/h seen with the basic MN patch (p<0.05). These findings were further supported by in vitro-in vivo mathematical correlation studies, indicating a 30% decrease in the required drug load in a basic patch design and a significant reduction in the necessary patch size.
Advancement in Emergency Opioid Overdose Treatment: Iontophoresis-Enabled Microneedle Skin Patch Delivering Naloxone
D.P. Culp Center Ballroom
The administration of naloxone for reversing opioid overdose is predominantly restricted to invasive injectables, due to its susceptibility to significant hepatic clearance when given traditionally. However, these delivery routes often entail discomfort and necessitate frequent injections to stabilize patients owing to NAL's short half-life. Introducing alternative delivery systems could prove advantageous, particularly if they offer a balance between sustained release characteristics and rapid onset. Intranasal delivery has been considered, but this has pitfalls including limited use due to damaged nasal mucosa, unpredictable responses, also sustained delivery is not feasible with this. Consequently, our study aims to develop a clinically feasible system of NAL offering clinically relevant attributes. In this study, we examined the transdermal delivery of naloxone using polymeric rapidly dissolving microneedles (MNs). We investigated how MN geometrical parameters affect NAL delivery and made pharmacokinetic predictions to anticipate in vivo delivery based on in vitro permeation profiles. Additionally, our investigation delved into the potential of iontophoretically driving ionized drug content within MN patches to augment the cumulative permeation of NAL. We refined the iontophoresis parameters by examining how changes in the strength of citrate phosphate buffer impact the drug release profile. Additionally, we investigated the potential benefits of integrating iontophoresis with higher drug loading to improve the patch's effectiveness. We explored the influence of current density, pH changes and competing ions on delivery profile from the iontophoresis coupled microneedle patches. Our observations showed a notable decrease in the lag time for delivering NAL to approximately 5-15 min using MN patches, compared to the typical 75 min with passive transdermal delivery. Increasing the length and density of MNs had a significant impact on the amount permeated and flux over a 24-hour period (p<0.05). Mathematical modeling of in-vitro release from the most effective patch highlighted the importance of needle base diameter and needle count in enhancing the systemic pharmacokinetics of NAL from the MN patches. This approach allowed us to predict an optimized patch design capable of replicating the clinical pharmacokinetics of NAL achieved with commercial devices. With the coupling of iontophoresis to the MN patches, the average cumulative permeation observed was 1331.44 ± 397.57 µg/cm2 within 1h while this was 103.00 ± 15.18 µg/cm2 with a basic patch. Similarly, the average flux over 1h was 619.09 ± 111.95 µg/cm2 with the iontophoresis coupled MN patch a remarkable increase over 102.98 ± 16.02 µg/cm2/h seen with the basic MN patch (p<0.05). These findings were further supported by in vitro-in vivo mathematical correlation studies, indicating a 30% decrease in the required drug load in a basic patch design and a significant reduction in the necessary patch size.