Clinically used amino-ester and amino-amide local anesthetics, such as bupivacaine and lidocaine, face two primary challenges: inadequate duration of action and nonselective action on both sensory and motor neurons, resulting in motor function loss alongside pain relief. In this work, we developed capsaicin-loaded melanin nanoparticles (Cap-MNPs) to address these two challenges. Capsaicin selectively acts on sensory neurons without affecting motor neurons, thereby achieving nociceptive-selective nerve blockade. Melanin is known for its exceptional biocompatibility, biodegradability, and abundance in pigmented human tissue. Melanin’s inherent chemical structure and hydrophobic nature enable the encapsulation and sustained release of amino-ester and amino-amide local anesthetics with aromatic rings through π–π interactions and hydrophobic interactions. The drug loading efficiency of Cap-MNPs was 82.99 ± 1.55%, the drug loading capacity was 67.47 ± 4.24%, and capsaicin was continuously released for more than 360 h. In rats, a single injection of Cap-MNPs containing 8.04 mg of capsaicin produced a sciatic sensory nerve block lasting for 6 h without causing any local toxicity and capsaicin-related systemic toxicity. Cap-MNPs show promise as clinically useful therapeutics for pain management.

中文翻译：

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载有辣椒素的黑色素纳米颗粒，用于长效伤害性选择性神经阻滞


临床上使用的氨基酯和氨基酰胺局麻药，如布比卡因和利多卡因，面临两个主要挑战：作用持续时间不足和对感觉和运动神经元的非选择性作用，导致运动功能丧失和疼痛缓解。在这项工作中，我们开发了载有辣椒素的黑色素纳米颗粒 （Cap-MNP） 来应对这两个挑战。辣椒素选择性地作用于感觉神经元，而不影响运动神经元，从而达到伤害性选择性神经阻滞。黑色素以其卓越的生物相容性、生物降解性和在色素沉着的人体组织中的丰度而闻名。黑色素固有的化学结构和疏水性使得氨基酯和氨基酰胺局麻药能够通过π-π相互作用和疏水相互作用与芳香环包封和持续释放。Cap-MNPs 的载药效率分别为 82.99 ± 1.55%，载药量分别为 67.47 ± 4.24%，辣椒素连续释放超过 360 h。在大鼠中，单次注射含有 8.04 mg 辣椒素的 Cap-MNPs 产生持续 6 h 的坐骨神经感觉神经阻滞，未引起任何局部毒性和辣椒素相关的全身毒性。Cap-MNP 有望成为临床上有用的疼痛管理疗法。