Journal
JOURNAL OF CONTROLLED RELEASE
Volume 207, Issue -, Pages 1-6Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2015.03.031
Keywords
Fecal incontinence; Hollow microneedle; Locally targeting delivery; Muscle contraction
Funding
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education [NRF-2014R1A1A2A16051484]
- Korean Health Technology R&D project, Ministry of Health & Welfare, Republic of Korea [HN10C0013]
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A hollow microneedle (HM) was prepared to deliver a phenylephrine (PE) solution into the anal sphincter muscle as a method for treating fecal incontinence. The goal of this study was the local targeted delivery of PE into the sphincter muscle through the perianal skin with minimal pain using hollow microneedles, resulting in the increase of resting anal sphincter pressure. PE was administered on the left and the right sides of the anus of a rat through the perianal skin using 1.5 mm long HM. An in vivo imaging system study was conducted after injection of Rhodamine B, and a histological study was performed after injection of gentian violet. The resting anal sphincter pressure in response to various drug doses was measured by using an air-charged catheter. Anal pressure change produced by HM administration was compared with change produced by intravenous injection (IV), subcutaneous (SC) injection and intramuscular (IM) injection. The change in mean blood pressure produced by HM administration as a function of PE dose was compared with change produced by PBS injection. A pharmacokinetic study of the new HM administration method was performed. A model drug solution was localized in the muscle layer under the perianal skin at the injection site and then diffused out over time. HM administration of PE induced significant contraction of internal anal sphincter pressure over 12 h after injection, and the maximum anal pressure was obtained between 5 and 6 h. Compared to IV, SC and IM treatments, HM treatment produced greater anal pressure. There was no increase in blood pressure after HM administration of PE within the range of predetermined concentration. Administration of 800 mu g/kg of PE using HM produced 0.81 +/- 0.38 h of t(max). Our study suggests that HM administration enables local delivery of a therapeutic dose of PE to the anal sphincter muscle layer with less pain. This new treatment has great potential as a clinical application because of the ease of the procedure, minimal pain, and dose-dependent response. (C) 2015 Elsevier B.V. All rights reserved.
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