Visser Johan Georg, Van Staden Anton Du Preez, Smith Carine
Department of Physiological Sciences, Stellenbosch University, Matieland, South Africa.
Front Pharmacol. 2019 Jan 25;10:22. doi: 10.3389/fphar.2019.00022. eCollection 2019.
With the effectiveness of therapeutic agents ever decreasing and the increased incidence of multi-drug resistant pathogens, there is a clear need for administration of more potent, potentially more toxic, drugs. Alternatively, biopharmaceuticals may hold potential but require specialized protection from premature degradation. Thus, a paralleled need for specialized drug delivery systems has arisen. Although cell-mediated drug delivery is not a completely novel concept, the few applications described to date are not yet ready for application, for various reasons such as drug-induced carrier cell death, limited control over the site and timing of drug release and/or drug degradation by the host immune system. Here, we present our hypothesis for a new drug delivery system, which aims to negate these limitations. We propose transport of nanoparticle-encapsulated drugs autologous macrophages polarized to M1 phenotype for high mobility and treated to induce transient phagosome maturation arrest. In addition, we propose a significant shift of existing paradigms in the study of host-microbe interactions, in order to study microbial host immune evasion and dissemination patterns for their therapeutic utilization in the context of drug delivery. We describe a system in which microbial strategies may be adopted to facilitate absolute control over drug delivery, and without sacrificing the host carrier cells. We provide a comprehensive summary of the lessons we can learn from microbes in the context of drug delivery and discuss their feasibility for therapeutic application. We then describe our proposed "synthetic microbe drug delivery system" in detail. In our opinion, this multidisciplinary approach may hold the solution to effective, controlled drug delivery.
随着治疗药物的有效性不断降低以及多重耐药病原体的发病率增加，显然需要使用更强效、潜在毒性更大的药物。或者，生物制药可能具有潜力，但需要专门保护以防止过早降解。因此，对专门的药物递送系统的需求也随之出现。尽管细胞介导的药物递送并非全新概念，但迄今为止所描述的少数应用由于各种原因，如药物诱导的载体细胞死亡、对药物释放部位和时间的控制有限以及/或者宿主免疫系统导致的药物降解，尚未准备好应用。在此，我们提出一种新的药物递送系统的假设，旨在消除这些限制。我们建议将纳米颗粒包裹的药物运输到极化至M1表型以实现高迁移率并经过处理以诱导吞噬体瞬时成熟停滞的自体巨噬细胞中。此外，我们建议在宿主 - 微生物相互作用的研究中对现有范式进行重大转变，以便研究微生物逃避宿主免疫和传播模式，从而在药物递送的背景下将其用于治疗。我们描述了一种系统，其中可以采用微生物策略来促进对药物递送的绝对控制，同时不牺牲宿主载体细胞。我们全面总结了在药物递送背景下可以从微生物中学到的经验教训，并讨论了它们在治疗应用中的可行性。然后我们详细描述了我们提出的“合成微生物药物递送系统”。我们认为，这种多学科方法可能是有效、可控药物递送的解决方案。
