Project Title

Microneedle-mediated transdermal delivery of naloxone hydrochloride for treatment of opioid addiction

Authors' Affiliations

Dorcas Frempong, Department of Pharmaceutical sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN Dhruv Mishra, Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ. Ashana Puri, Department of Pharmaceutical Sciences,College of Pharmacy, East Tennessee State University, Johnson City, TN.

Faculty Sponsor’s Department

Pharmaceutical Sciences

Type

Oral Competitive

Classification of First Author

Pharmacy Student

Project's Category

Public Health, Quality of Life

Abstract Text

Opioid addiction is a serious national crisis impacting public health. Naloxone is a potent opioid antagonist administered to reverse the effects of opioid overdose. It is currently administered as an intravenous, intramuscular, subcutaneous injection and intranasal spray. The short duration of action of naloxone results in requirement of frequent re-dosing, especially in cases of larger overdoses, which may impact successful outcomes, especially when drug administration is provided by non-medical personnel as in case of intranasal sprays. These weaknesses necessitate the development of a non-injectable dosage form that has a rapid onset and extended duration of action. Delivery of drugs via skin is an attractive alternative that provides these benefits. Our study aimed to assess the effect of microneedles on the amount and lag time of permeation of naloxone across skin. In vitro permeation studies were performed to assess the delivery of naloxone through dermatomed porcine ear skin using Franz Diffusion cells. The donor and receptor chamber of the cells contained the drug solution and phosphate buffered saline, respectively. The receptor was sampled until 6 h and analyzed using HPLC. The permeation of naloxone across intact (passive) and microneedle-treated (Dr. Pen™ Ultima A6) skin was evaluated. Two microporation conditions with donor concentration of 10 mg/mL were investigated: needle lengths (500 µm and 250 µm) for 1 minute and 500 µm needle length for different durations (1 and 2 minutes). Further, the effect of application of different naloxone concentrations (10 and 20 mg/mL) on skin treated with 500 µm microneedles for 2 minutes was also tested. One-way ANOVA was applied to ascertain statistical difference between the different test groups. The amount of passive permeation after 6 h and lag time for naloxone was observed to be 8.251.06 µg/cm2 and88.58 ± 3.05 min, respectively. One minute treatment with 500 µm needles significantly enhanced the permeation to 463.24 ± 30.21 µg/cm2 and reduced the lag time to 15.90 ± 1.63 min (p0.05). Microneedles were found to enhance the permeation of naloxone across skin. The observation of quick onset of drug permeation in the in vitro settings is very encouraging and future studies would focus on developing a microneedle patch for quick onset and extended drug release.

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Microneedle-mediated transdermal delivery of naloxone hydrochloride for treatment of opioid addiction

Opioid addiction is a serious national crisis impacting public health. Naloxone is a potent opioid antagonist administered to reverse the effects of opioid overdose. It is currently administered as an intravenous, intramuscular, subcutaneous injection and intranasal spray. The short duration of action of naloxone results in requirement of frequent re-dosing, especially in cases of larger overdoses, which may impact successful outcomes, especially when drug administration is provided by non-medical personnel as in case of intranasal sprays. These weaknesses necessitate the development of a non-injectable dosage form that has a rapid onset and extended duration of action. Delivery of drugs via skin is an attractive alternative that provides these benefits. Our study aimed to assess the effect of microneedles on the amount and lag time of permeation of naloxone across skin. In vitro permeation studies were performed to assess the delivery of naloxone through dermatomed porcine ear skin using Franz Diffusion cells. The donor and receptor chamber of the cells contained the drug solution and phosphate buffered saline, respectively. The receptor was sampled until 6 h and analyzed using HPLC. The permeation of naloxone across intact (passive) and microneedle-treated (Dr. Pen™ Ultima A6) skin was evaluated. Two microporation conditions with donor concentration of 10 mg/mL were investigated: needle lengths (500 µm and 250 µm) for 1 minute and 500 µm needle length for different durations (1 and 2 minutes). Further, the effect of application of different naloxone concentrations (10 and 20 mg/mL) on skin treated with 500 µm microneedles for 2 minutes was also tested. One-way ANOVA was applied to ascertain statistical difference between the different test groups. The amount of passive permeation after 6 h and lag time for naloxone was observed to be 8.251.06 µg/cm2 and88.58 ± 3.05 min, respectively. One minute treatment with 500 µm needles significantly enhanced the permeation to 463.24 ± 30.21 µg/cm2 and reduced the lag time to 15.90 ± 1.63 min (p0.05). Microneedles were found to enhance the permeation of naloxone across skin. The observation of quick onset of drug permeation in the in vitro settings is very encouraging and future studies would focus on developing a microneedle patch for quick onset and extended drug release.

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