TY - JOUR
T1 - Mechanistic modeling-guided optimization of microneedle-based skin patch for rapid transdermal delivery of naloxone for opioid overdose treatment
AU - Tijani, Akeemat
AU - Dogra, Prashant
AU - Peláez, Maria J.
AU - Wang, Zhihui
AU - Cristini, Vittorio
AU - Puri, Ashana
N1 - Funding Information:
This research work was partially funded by the American Association of Colleges of Pharmacy via New Investigator Award 2020–2021 (AP). This research has also been supported in part by the Cockrell Foundation (PD, VC), and by the National Science Foundation Grant DMS-1930583 (ZW, VC), and the National Institutes of Health (NIH) Grants 1R01CA253865 (ZW, VC), 1U01CA196403 (ZW, VC), 1U01CA213759 (ZW, VC), 1R01CA226537 (ZW, VC), and 1R01CA222007 (ZW, VC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022, Controlled Release Society.
PY - 2022/7/25
Y1 - 2022/7/25
N2 - Naloxone, an FDA-approved opioid inhibitor, used to reverse opioid overdose complications has up till date faced challenges associated with its delivery. Limitations include the use of invasive delivery forms and the need for frequent redosing due to its short half-life. The goal of the current study was to design a transdermal rapidly dissolving polymeric microneedle (MN) patch with delivery and pharmacokinetic properties comparable to that seen with the commercially available NAL products, eliminating their delivery limitations. Patches of varying dimensions (500 µm; 100 array,800 µm; 100array, and 600 µm; 225 array) were fabricated to evaluate the effect of increasing MN length, and density (no. of needles/unit area) on drug release. Drug dose in each of these patches was 17.89 ± 0.23 mg, 17.2 ± 0.77 mg, and 17.8 ± 1.01 mg, respectively. Furthermore, the insertion efficiency of each of the MN patches was 94 ± 4.8%, 90.6 ± 1.69%, and 96 ± 1.29%, respectively. Compared to passive permeation, a reduced lag time of about 5–15 min was observed with a significant drug flux of 15.09 ± 7.68 gμ/cm2/h seen in the first 1 h (p < 0.05) with the array of 100 needles (500 µm long). Over 24 h, a four and ten-fold increase in permeation was seen with the longer length and larger density MN patch, respectively, when compared to the 500 µm (100 array) patch. Model simulations and analyses revealed the significance of needle base diameter and needle count in improving systemic pharmacokinetics of NAL. Graphical abstract: [Figure not available: see fulltext.].
AB - Naloxone, an FDA-approved opioid inhibitor, used to reverse opioid overdose complications has up till date faced challenges associated with its delivery. Limitations include the use of invasive delivery forms and the need for frequent redosing due to its short half-life. The goal of the current study was to design a transdermal rapidly dissolving polymeric microneedle (MN) patch with delivery and pharmacokinetic properties comparable to that seen with the commercially available NAL products, eliminating their delivery limitations. Patches of varying dimensions (500 µm; 100 array,800 µm; 100array, and 600 µm; 225 array) were fabricated to evaluate the effect of increasing MN length, and density (no. of needles/unit area) on drug release. Drug dose in each of these patches was 17.89 ± 0.23 mg, 17.2 ± 0.77 mg, and 17.8 ± 1.01 mg, respectively. Furthermore, the insertion efficiency of each of the MN patches was 94 ± 4.8%, 90.6 ± 1.69%, and 96 ± 1.29%, respectively. Compared to passive permeation, a reduced lag time of about 5–15 min was observed with a significant drug flux of 15.09 ± 7.68 gμ/cm2/h seen in the first 1 h (p < 0.05) with the array of 100 needles (500 µm long). Over 24 h, a four and ten-fold increase in permeation was seen with the longer length and larger density MN patch, respectively, when compared to the 500 µm (100 array) patch. Model simulations and analyses revealed the significance of needle base diameter and needle count in improving systemic pharmacokinetics of NAL. Graphical abstract: [Figure not available: see fulltext.].
KW - Microneedles
KW - Naloxone
KW - Opioid
KW - Polyvinylpyrrolidone (PVP)
KW - Transdermal delivery
KW - Analgesics, Opioid
KW - Humans
KW - Opiate Overdose
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U2 - 10.1007/s13346-022-01202-w
DO - 10.1007/s13346-022-01202-w
M3 - Article
C2 - 35879533
SN - 2190-393X
VL - 13
SP - 320
EP - 338
JO - Drug Delivery and Translational Research
JF - Drug Delivery and Translational Research
IS - 1
ER -