Diclofenac Enables Unprecedented Week-Long Microneedle-Enhanced Delivery of a Skin Impermeable Medication in Humans

• Published in: Pharmaceutical research 2013-08, Vol.30 (8), p.1947-1955
• Main Authors: Brogden, Nicole K., Banks, Stan L., Crofford, Leslie J., Stinchcomb, Audra L.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Diclofenac - metabolism; Drug delivery systems; Drug Delivery Systems - methods; Female; Humans; Male; Medical Law; Medical sciences; Microinjections - methods; Naltrexone - administration & dosage; Naltrexone - blood; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - blood; Needles; Neuropharmacology; Pharmaceutical sciences; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Research Paper; Skin Absorption - drug effects; Young Adult
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-013-1036-1

Purpose Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. The purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans. Methods Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application. Results Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n  = 6), vs. 72 h in Group 2 (placebo + naltrexone, n  = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores). Conclusion This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases.