Kumar Pradeep
Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Front Bioeng Biotechnol. 2020 Sep 25;8:577172. doi: 10.3389/fbioe.2020.577172. eCollection 2020.
After more than 225 days of the first reports of the novel coronavirus from China, COVID-19 pandemic is still on surge. The search for an effective and efficient therapeutic and pharmaceutical intervention is as important and urgent now as it was on Day 1. Majority of the efforts in this direction are toward finding small molecule interventions via repurposing or redirecting the therapeutic approaches. This hypothesis proposes a physical intervention approach directed toward rescuing the complex lung pathology observed in COVID-19 related acute respiratory distress syndrome (CARDS). The loss of content as well as the synthesis and turnover of the surfactant in ARDS has been termed as a "collateral damage." A synergistic, early stage, cost-effective, pharmaceutically viable, safe, and immediately available solution is hence required. The effectiveness of exogenous surfactant treatment in ARDS has been marred with several limitations as pointed out in various clinical trials and require revised protocols related to surfactant dose and mode of delivery. This hypothesis proposes aerosolized surfactant delivery taking the optimal dosing and coating costs into account along with co-delivery of ambroxol to provide synergistic benefits. Ambroxol is reported to have anti-inflammatory, -oxidant, -viral, and -bacterial activities and has a direct impact on the production and secretion of the surfactant from the alveolar Type 2 cells. If aerosolized, atomized, or nebulized in the form of ambroxol-loaded phospholipid nanovesicles at the early stages of ARDS, depleted surfactant levels may be reinstated and surfactant turnover can be initiated and maintained. The ability to deliver both the components in aerosolized-nebulized form may have a huge impact on alleviating the healthcare burden in low resource settings where the availability of ventilators is limited. In conclusion, the surfactant-ambroxol co-aerosolized intervention approach hypothesized here has implications reaching to clinical and pharmaceutical translation worldwide.
自中国首次报告新型冠状病毒已过去225多天，新冠疫情仍在激增。如今，寻找有效且高效的治疗和药物干预措施与疫情爆发首日一样重要和紧迫。在这方面的大多数努力都致力于通过重新利用或调整治疗方法来寻找小分子干预措施。本假说提出了一种物理干预方法，旨在挽救新冠相关急性呼吸窘迫综合征（CARDS）中观察到的复杂肺部病理状况。ARDS中表面活性剂含量的丧失以及其合成和周转被称为“附带损害”。因此，需要一种协同、早期、经济高效、具有药物可行性、安全且立即可用的解决方案。正如各种临床试验所指出的，外源性表面活性剂治疗ARDS的有效性存在若干局限性，需要修订与表面活性剂剂量和给药方式相关的方案。本假说提出雾化输送表面活性剂，同时考虑最佳给药剂量和包衣成本，并联合氨溴索给药以提供协同效益。据报道，氨溴索具有抗炎、抗氧化、抗病毒和抗菌活性，并且对肺泡II型细胞表面活性剂的产生和分泌有直接影响。如果在ARDS早期以载有氨溴索的磷脂纳米囊泡形式进行雾化、喷雾或喷射，可恢复已耗尽的表面活性剂水平，并启动和维持表面活性剂周转。以雾化-喷雾形式输送这两种成分的能力可能对减轻资源匮乏地区的医疗负担产生巨大影响，因为这些地区呼吸机的可用性有限。总之，本文提出的表面活性剂-氨溴索联合雾化干预方法对全球临床和药物转化具有重要意义。
