Local transdermal delivery of phenylephrine to the anal sphincter muscle using microneedles

We propose pretreatment using microneedles to increase perianal skin permeability for locally targeted delivery of phenylephrine (PE), a drug that increases resting anal sphincter pressure to treat fecal incontinence. Microneedle patches were fabricated by micromolding poly-lactic-acid. Pre-treatment of human cadaver skin with microneedles increased PE delivery across the skin by up to 10-fold in vitro. In vivo delivery was assessed in rats receiving treatment with or without use of microneedles and with or without PE. Resting anal sphincter pressure was then measured over time using water-perfused anorectal manometry. For rats pretreated with microneedles, topical application of 30% PE gel rapidly increased the mean resting anal sphincter pressure from 7 ± 2 cmH2O to a peak value of 43 ± 17 cmH2O after 1 h, which was significantly greater than rats receiving PE gel without microneedle pretreatment. Additional safety studies showed that topically applied green fluorescent protein—expressing E. coli penetrated skin pierced with 23- and 26-gauge hypodermic needles, but E. coli was not detected in skin pretreated with microneedles, which suggests that microneedle-treated skin may not be especially susceptible to infection. In conclusion, this study demonstrates local transdermal delivery of PE to the anal sphincter muscle using microneedles, which may provide a novel treatment for fecal incontinence.

Diagram of locally targeted delivery of PE into anal sphincter muscle through perianal skin using microneedles. Microneedles generate holes on perianal skin to make local delivery pathways for PE to the sphincter muscles. 1. External sphincter muscle. 2. Internal sphincter muscle. 3. Anal canal. 4. Rectum. 5. Path of PE delivery. 6. Microneedles. (The picture of the anus is copyrighted by the Mayo Foundation for Medical Education and Research and is used with permission.)Figure optionsDownload as PowerPoint slide