中文摘要：随着全球抗生素耐药性的出现和蔓延以及寻找更安全的替代品的需要，探索噬菌体在细菌感染治疗中的应用（噬菌体疗法）又重新兴起。尽管现代噬菌体疗法已经取得了长足的进步，许多疗效研究都证明了这一点，但事实上，迄今为止，噬菌体疗法尚未获得监管部门批准用于人类（同情性使用除外）。因此，要打入临床市场，需要认真解决这些障碍。纳米技术是一种理想而强大的工具，用于克服噬菌体制剂的药理学障碍（稳定性低、体内滞留差、靶向递送、免疫系统中和等）。已有许多关于纳米技术和噬菌体的综述文章，但这些文章主要侧重于强调裂解型和温和型噬菌体在纳米医学不同领域的应用，如纳米探针、纳米传感器、癌症诊断、癌细胞靶向、通过噬菌体受体给药、噬菌体展示等；而专门侧重于使用纳米技术来严格改进噬菌体治疗的综述则很有限。此外，这些综述主要集中在讨论封装作为提高噬菌体在体内的稳定性和停留的主要方法。随着纳米技术领域取得新进展，应用方法从单纯的封装扩展到最近采用的新策略。本综述详细介绍了最新策略，包括1）脂质体纳米载体（脂质体、转移体等）的使用；2）采用基于微流控技术的表面修饰方法，进一步提高噬菌体脂质体的效率和稳定性；3）融合微流体与纳米乳化方法，生产多种对大小、形状和液滴形态具有独特控制的乳剂(适用于噬菌体混合物)；4）静电纺丝法制备的噬菌体纳米纤维和先进的核壳纳米纤维，用于即时、双相和延迟释放系统；5）智能释放给药平台，可在需要时更好地控制给药量和噬菌体释放。所有这些新进展均旨在为治疗性噬菌体制剂创建合适的外壳系统，同时解决噬菌体治疗的多个问题，即提高噬菌体稳定性和滴度、改善体内滞留时间、作为合适的输送系统在感染靶点持续释放、提高对生物膜的渗透性、防止免疫细胞攻击。因此，本综述旨在全面了解各种基于纳米技术的方法的最新进展（2010年以后），以解决与噬菌体治疗相关的问题。这对提高整体治疗指标和噬菌体治疗的成功率至关重要，以备将来临床批准。
外文摘要：With the emergence and spread of global antibiotic resistance and the need for searching safer alternatives, there has been resurgence in exploring the use of bacteriophages in the treatment of bacterial infections referred as phage therapy. Although modern phage therapy has come a long way as demonstrated by numerous efficacy studies but the fact remains that till date, phage therapy has not received regulatory approval for human use (except for compassionate use).Thus, to hit the clinical market, the roadblocks need to be seriously addressed and gaps mended with modern solution based technologies. Nanotechnology represents one such ideal and powerful tool for overcoming the pharmacological barriers (low stability, poor in-vivo retention, targeted delivery, neutralisation by immune system etc.) of administered phage preparations. In literature, there are many review articles on nanotechnology and bacteriophages but these are primarily focussed on highlighting the use of lytic and temperate phages in different fields of nano-medicine such as nanoprobes, nanosensors, cancer diagnostics, cancer cell targeting, drug delivery through phage receptors, phage display etc. Reviews specifically focused on the use of nanotechnology driven techniques strictly to improve phage therapy are however limited. Moreover, these review if present have primarily focussed on discussing encapsulation as a primary method for improving the stability and retention of phage(s) in the body. With new advances made in the field of nanotechnology, approaches extend from mere encapsulation to recently adopted newer strategies. The present review gives a detailed insight into the more recent strategies which include 1) use of lipid based nano-carriers (liposomes, transfersomes etc.) 2) adopting microfluidic based approach, surface modification methods to further enhance the efficiency and stability of phage loaded liposomes 3) Nano- emulsification approach with integration of microfluidics for producing multiple emulsions (suitable for phage cocktails) with unique control over size, shape and drop morphology 4) Phage loaded nanofibers produced by electro-spinning and advanced core shell nanofibers for immediate, biphasic and delayed release systems and 5) Smart release drug delivery platforms that allow superior control over dosing and phage release as and when required. All these new advances are aimed at creating a suitable housing system for therapeutic bacteriophage preparations while targeting the multiple issues of phage therapy i.e., improving phage stability and titers, improving in-vivo retention times, acting as suitable delivery systems for sustained release at target site of infection, improved penetration into biofilms and protection from immune cell attack. The present review thus aims at giving a complete insight into the recent advances (2010 onwards) related to various nanotechnology based approaches to address the issues pertaining to phage therapy. This is essential for improving the overall therapeutic index and success of phage therapy for future clinical approval.
外文关键词：nanotechnology；phage therapy；nano-emulsification；encapsulation；liposome; nanofibers；pharmacological barriers
作者：Kaur, S；Kumari, A；Negi, AK；Galav, V；Thakur, S；Agrawal, M；Sharma, V
作者单位：Dr Rajendra Prasad Govt Med Coll；Post Grad Inst Vet Educ & Res RAJUVAS；Kumaun Univ
期刊名称：FRONTIERS IN PHARMACOLOGY
期刊影响因子：4.225
出版年份：2021
出版刊次：
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