Analgesic Microneedle Patch for Neuropathic Pain Therapy

被引:121
作者
Xie, Xi [1 ,2 ,3 ]
Pascual, Conrado [1 ,4 ]
Lieu, Christopher [1 ]
Oh, Seajin [1 ]
Wang, Ji [5 ]
Zou, Bende [1 ]
Xie, Julian [1 ]
Li, Zhaohui [1 ]
Xie, James [1 ]
Yeomans, David C. [4 ]
Wu, Mei X. [5 ]
Xie, Xinmin Simon [1 ,4 ]
机构
[1] AfaSci Res Labs, Redwood City, CA 94063 USA
[2] Sun Yat Sen Univ, Sch Elect & Informat Technol, Guangzhou 510275, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, State Key Lab Optoelect Mat & Technol, Guangzhou 510275, Guangdong, Peoples R China
[4] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA
[5] Harvard Med Sch, Dept Dermatol, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA
关键词
microneedle; CGRP antagonist peptide; neuropathic pain; analgesia; drug delivery; GENE-RELATED PEPTIDE; ORAL OPIOID THERAPY; SUBSTANCE-P; DRUG; DELIVERY; MODEL; LIDOCAINE; CGRP; ANTAGONISTS; GABAPENTIN;
D O I
10.1021/acsnano.6b06104
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.
引用
收藏
页码:395 / 406
页数:12
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