Himanshu Kathuria1, Hairui Li1, Jing Pan1, Seng Han Lim1, Jaspreet Singh Kochhar1, Chunyong Wu2, Lifeng Kang3. 1. Department of Pharmacy, National University of Singapore, Singapore, 117543, Singapore. 2. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China. 3. Department of Pharmacy, National University of Singapore, Singapore, 117543, Singapore. lkang@nus.edu.sg.
Abstract
PURPOSE: Current topical treatments using lidocaine (LD) for analgesia have limited applications due to their delayed analgesic actions, resulted from slow drug permeation through skin. The aim of this study is to fabricate a large size microneedle (MN) array patch containing LD, with fast onset of action, for the treatment of acute and chronic pain. METHODS: The MN patch was developed through photolithography and tested for its mechanical characteristics. In vitro and in vivo skin permeation, plasma pharmacokinetics, histology and skin irritation testing have also been performed for the MN patches. RESULTS: The MN have a mechanical strength of 10-30 N and more than 90% of the microneedles on the patch penetrated skin. It was shown that LD permeated through skin within 5 min of patch application. Subsequently, the in vivo skin permeation study using a porcine model showed that LD administrated by the MN patch was able to achieve the therapeutic level locally within 10 min and sustained for 8 h. It shows most of the drug diffuses perpendicularly against skin, with little lateral diffusion. After skin permeation LD remains within skin and unquantifiable amount of LD was found in the plasma of the pigs. Minor skin irritations were observed after 6 h of microneedle contact. However, the skin irritations resolved within 1 day following the removal of MN patch. CONCLUSION: The large size MN patches showed fast onset and sustained delivery of LD through skin, potentially useful to increase the application scope of topical LD for pain management.
PURPOSE: Current topical treatments using lidocaine (LD) for analgesia have limited applications due to their delayed analgesic actions, resulted from slow drug permeation through skin. The aim of this study is to fabricate a large size microneedle (MN) array patch containing LD, with fast onset of action, for the treatment of acute and chronic pain. METHODS: The MN patch was developed through photolithography and tested for its mechanical characteristics. In vitro and in vivo skin permeation, plasma pharmacokinetics, histology and skin irritation testing have also been performed for the MN patches. RESULTS: The MN have a mechanical strength of 10-30 N and more than 90% of the microneedles on the patch penetrated skin. It was shown that LD permeated through skin within 5 min of patch application. Subsequently, the in vivo skin permeation study using a porcine model showed that LD administrated by the MN patch was able to achieve the therapeutic level locally within 10 min and sustained for 8 h. It shows most of the drug diffuses perpendicularly against skin, with little lateral diffusion. After skin permeation LD remains within skin and unquantifiable amount of LD was found in the plasma of the pigs. Minor skin irritations were observed after 6 h of microneedle contact. However, the skin irritations resolved within 1 day following the removal of MN patch. CONCLUSION: The large size MN patches showed fast onset and sustained delivery of LD through skin, potentially useful to increase the application scope of topical LD for pain management.
Entities:
Keywords:
drug diffusion; lidocaine; microneedle; pain; skin permeation; transdermal patch
Authors: Xiao Peng Zhang; Bao Li Zhang; Bo Zhi Chen; Ze Qiang Zhao; Wen Min Fei; Yong Cui; Xin Dong Guo Journal: Drug Deliv Transl Res Date: 2021-11-06 Impact factor: 4.617