Crowe Kaytlyn M, Siddiqui Zain, Harbour Victoria, Kim KaKyung, Syed Shareef, Paul Reshma, Roy Abhishek, Naik Ruhi, Mitchell Kayla, Mahajan Aryan, Sarkar Biplab, Kumar Vivek A
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102, United States.
Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102, United States.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7858-7864. doi: 10.1021/acsabm.0c01016. Epub 2020 Nov 4.
The opioid epidemic in the United States is a serious public health crisis affecting over 1.7 million Americans. In the last two decades, almost 450 000 people have died from an opioid overdose, with nearly 20% of these deaths occurring in 2017 and 2018 alone. During an overdose, overstimulation of the μ-opioid receptor leads to severe and potentially fatal respiratory depression. Naloxone is a competitive μ-opioid-receptor antagonist that is widely used to displace opioids and rescue from an overdose. Here, we describe the development of a slow-release, subcutaneous naloxone formulation for potential management of opioid overdose, chronic pain, and opioid-induced constipation. Naloxone is loaded into self-assembling peptide hydrogels for controlled drug release. The mechanical, chemical, and structural properties of the nanofibrous hydrogel enable subcutaneous administration and slow, diffusion-based release kinetics of naloxone over 30 days in vitro. The naloxone hydrogel scaffold showed cytocompatibility and did not alter the β-sheet secondary structure or thixotropic properties characteristic of self-assembling peptide hydrogels. Our results show that this biocompatible and injectable self-assembling peptide hydrogel may be useful as a vehicle for tunable, sustained release of therapeutic naloxone. This therapy may be particularly suited for preventing renarcotization in patients who refuse additional medical assistance following an overdose.
美国的阿片类药物泛滥是一场严重的公共卫生危机，影响着超过170万美国人。在过去二十年中，近45万人死于阿片类药物过量，其中仅2017年和2018年就有近20%的死亡病例。在药物过量期间，μ-阿片受体的过度刺激会导致严重且可能致命的呼吸抑制。纳洛酮是一种竞争性μ-阿片受体拮抗剂，广泛用于取代阿片类药物并抢救过量用药者。在此，我们描述了一种用于潜在治疗阿片类药物过量、慢性疼痛和阿片类药物引起的便秘的缓释皮下纳洛酮制剂的研发情况。纳洛酮被载入自组装肽水凝胶中以实现药物的控释。纳米纤维水凝胶的机械、化学和结构特性使其能够进行皮下给药，并在体外30天内实现基于扩散的纳洛酮缓慢释放动力学。纳洛酮水凝胶支架显示出细胞相容性，且不会改变自组装肽水凝胶的β-折叠二级结构或触变性。我们的结果表明，这种生物相容性且可注射的自组装肽水凝胶可能作为治疗性纳洛酮可调谐、持续释放的载体。这种疗法可能特别适合防止在过量用药后拒绝额外医疗救助的患者再次成瘾。
