Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Medicine, Chung Ang University, Dongjak-gu, Seoul 156-861, South Korea.
J Control Release. 2015 Jun 10;207:1-6. doi: 10.1016/j.jconrel.2015.03.031. Epub 2015 Mar 28.
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 1.5mm 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 12h after injection, and the maximum anal pressure was obtained between 5 and 6h. 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 800μg/kg of PE using HM produced 0.81±0.38h of tmax. 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.
一种空心微针（HM）被制备用于将苯肾上腺素（PE）溶液递送到肛门括约肌肌肉中，作为治疗粪便失禁的方法。本研究的目的是通过肛周皮肤使用空心微针以最小的疼痛将 PE 局部递送到括约肌肌肉中，从而增加静息肛门括约肌压力。通过肛周皮肤用 1.5mm 长的 HM 在大鼠肛门的左侧和右侧给予 PE。在注射罗丹明 B 后进行体内成像系统研究，并在注射龙胆紫后进行组织学研究。通过使用空气充气管测量对各种药物剂量的静息肛门括约肌压力的响应。将 HM 给药引起的肛门压力变化与静脉内（IV）注射、皮下（SC）注射和肌肉内（IM）注射引起的变化进行比较。将 HM 给药引起的平均血压变化与 PBS 注射引起的变化进行比较。进行了新的 HM 给药方法的药代动力学研究。模型药物溶液定位于注射部位肛周皮肤的肌肉层中，然后随时间扩散。HM 给药后，PE 在注射后 12 小时内引起内肛门括约肌压力的显著收缩，最大肛门压力在 5 至 6 小时之间获得。与 IV、SC 和 IM 治疗相比，HM 治疗产生更大的肛门压力。在预定浓度范围内，PE 的 HM 给药后血压没有升高。使用 HM 给予 800μg/kg 的 PE 产生 0.81±0.38h 的 tmax。我们的研究表明，HM 给药能够将治疗剂量的 PE 局部递送到肛门括约肌肌肉层，疼痛较小。由于该方法的简便性、最小的疼痛和剂量依赖性反应，这种新的治疗方法具有很大的临床应用潜力。
