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All disease, but especially non-communicable diseases, are related to dysfunction of one or more regulatory systems. In developing countries, long-term management of patients with chronic diseases has many challenges and is generally not financially viable, but Africa in particular, which is rich in diverse ethnomedicines presents a more feasible long-term therapeutic approach in this niche. However, despite comprehensive preclinical investigations on numerous plant-derived candidate medicines, only a small portion of these reach the patient as recognised medicines. In this review, we use the example of rooibos (Aspalathus linearis (Burm.f.) R. Dahlgren)–which is globally consumed as aromatic, caffeine-free tea–to illustrate the hurdles that need to be overcome in the low-to middle-income countries, before progression of ethnomedicines to official treatment regimens can be achieved. In terms of methodology, regulatory system focused rooibos papers indexed on PubMed for the past three decades (n = 112) were accessed. Papers reporting duplication of previous results were excluded, as well as review papers. Topics covered includes the high standard of ethnomedicine drug discovery and efficacy testing research performed in Africa (and South Africa in particular in the case of rooibos), the potential bias in terms of preclinical research focus, ethnomedicine ownership and the requirement for independent clinical trial coordination and/or management.

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 in vivo 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 in vivo 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 inside 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 in vivo 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.