Pocketed microneedles for rapid delivery of a liquid-state botulinum toxin A formulation into human skin.
Pocketed microneedles for rapid delivery of a liquid-state botulinum toxin A formulation into human skin.
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DOI：
10.1016/j.jconrel.2012.11.010
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发表时间：
2013-01-28
期刊：
影响因子：
--
通讯作者：
Coulman SA
中科院分区：
文献类型：
--
作者：
Torrisi BM;Zarnitsyn V;Prausnitz MR;Anstey A;Gateley C;Birchall JC;Coulman SA
肉毒杆菌毒素A （BT）用于治疗原发性局灶性多汗症，这是一种以分泌汗腺过度活动为特征的慢性衰弱疾病。考虑到全身性毒性，BT需要通过局部注射给药，在多汗症的情况下，这意味着由熟练的临床医生每隔6个月进行多次皮内注射。本研究探讨了一种装载液体的口袋微针装置将肉毒毒素a输送到人体真皮的潜力，目的是减少患者的疼痛，提高治疗的靶向性和简化给药程序。最初，β-半乳糖苷酶被用作BT的可检测模型，以(i)可视化微针的液体负载，（ii）确定液体制剂在设备上的停留时间，（iii）量化负载剂量。一个由五个不锈钢口袋微针组成的阵列被证明具有足够的能力来输送治疗剂量的强效BT蛋白。微针介导的β-半乳糖苷酶和甲醛灭活肉毒杆菌类毒素皮内递送显示在真皮内有效沉积和随后扩散。这项研究首次描述了将液体配方装入口袋的微针输送到人体皮肤中，并说明了这种系统在皮肤给药如BT等强效蛋白质方面的潜力。一种临床上合适的BT微针输送系统可能会对医疗和化妆品行业产生重大影响。
Botulinum toxin A (BT) is used therapeutically for the treatment of primary focal hyperhidrosis, a chronic debilitating condition characterised by over-activity of the eccrine sweat glands. Systemic toxicity concerns require BT to be administered by local injection, which in the case of hyperhidrosis means multiple painful intradermal injections by a skilled clinician at 6-monthly intervals. This study investigates the potential of a liquid-loaded pocketed microneedle device to deliver botulinum toxin A into the human dermis with the aim of reducing patient pain, improving therapeutic targeting and simplifying the administration procedure. Initially, β-galactosidase was employed as a detectable model for BT to (i) visualise liquid loading of the microneedles, (ii) determine residence time of a liquid formulation on the device and (iii) quantify loaded doses. An array of five stainless steel pocketed microneedles was shown to possess sufficient capacity to deliver therapeutic doses of the potent BT protein. Microneedle-mediated intradermal delivery of β-galactosidase and formaldehyde-inactivated botulinum toxoid revealed effective deposition and subsequent diffusion within the dermis. This study is the first to characterise pocketed microneedle delivery of a liquid formulation into human skin and illustrates the potential of such systems for the cutaneous administration of potent proteins such as BT. A clinically appropriate microneedle delivery system for BT could have a significant impact in both the medical and cosmetic industries.
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作者：
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