Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.
Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.
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DOI：
10.1016/j.actbio.2018.05.038
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发表时间：
2018-07-01
影响因子：
9.7
通讯作者：
Nair LS
中科院分区：
文献类型：
--
作者：
Khanal M;Gohil SV;Kuyinu E;Kan HM;Knight BE;Baumbauer KM;Lo KW;Walker J;Laurencin CT;Nair LS
肌肉骨骼疼痛是一个主要的健康问题，它由外科手术（如全膝关节和/或髋关节置换以及肩袖修复）以及非外科疾病（如交感神经介导的疼痛综合征和枕神经痛）引起。局部麻醉剂、阿片类药物或皮质类固醇目前用于肌肉骨骼疾病的疼痛管理。尽管局部麻醉剂是非常受欢迎的，但需要多次给药存在明显的缺点。开发能够在注射部位长时间释放局部麻醉剂的独特给药系统可以显著提高治疗效果和患者的舒适度。本研究的目的是评估一种可注射的局部麻醉纳米复合载体提供持续镇痛效果的功效。该纳米复合载体是通过将局部麻醉剂罗哌卡因包裹在脂质纳米胶囊（LNC - 罗哌卡因）中，并将纳米胶囊掺入酶交联的乙二醇壳聚糖（0.3GC）水凝胶中而开发的。低温扫描电子显微镜（Cryo SEM）图像显示能够在水凝胶内分布纳米胶囊，而不会对其形态产生不利影响。研究证明了从纳米复合载体在体外和体内实现亲脂性分子持续释放的可行性。采用大鼠慢性坐骨神经缩窄损伤（CCI）疼痛模型，通过热缩足反射潜伏期（TWL）来评估纳米复合载体的功效。与对照组相比，负载罗哌卡因和地塞米松的纳米复合载体在至少7天内疼痛反应有显著改善。研究证明了这些纳米复合载体在术后疼痛和神经性疼痛方面的临床潜力。
Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadvantages. Development of unique delivery systems that can deliver local anesthetics at the injection site for prolonged time could significantly enhance the therapeutic efficacy and patient comfort. The goal of the present study is to evaluate the efficacy of an injectable local anesthetic nanocomposite carrier to provide sustained analgesic effect. The nanocomposite carrier was developed by encapsulating ropivacaine, a local anesthetic, in lipid nanocapsules (LNC-Rop), and incorporating the nanocapsules in enzymatically crosslinked glycol chitosan (0.3GC) hydrogels. Cryo Scanning Electron Microscopic (Cryo SEM) images showed the ability to distribute the LNCs within the hydrogel without adversely affecting their morphology. The study demonstrated the feasibility to achieve sustained release of lipophilic molecules from the nanocomposite carrier in vitro and in vivo. A rat chronic constriction injury (CCI) pain model was used to evaluate the efficacy of the nanocomposite carrier using thermal paw withdrawal latency (TWL). The nanocomposite carriers loaded with ropivacaine and dexamethasone showed significant improvement in pain response compared to the control groups for at least 7 days. The study demonstrated the clinical potential of these nanocomposite carriers for post-operative and neuropathic pain.
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影响因子：
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作者：
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通讯作者：
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DOI：
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