Band 8, Heft 3

The diagnosis and management of pneumococcal disease remains challenging, in particular in children who often are asymptomatic carriers, and in low-income countries with a high morbidity and mortality from febrile illnesses where the broad range of bacterial, viral and parasitic cases are in contrast to limited, diagnostic resources. Integration of multiple markers into a single, rapid test is desirable in such situations. Likewise, the development of multiparameter tests for relevant arrays of pathogens is important to avoid overtreatment of febrile syndromes with antibiotics. Miniaturization of tests through use of micro- and nanotechnologies combines several advantages: miniaturization reduces sample requirements, reduces the use of consumables and reagents leading to a reduction in costs, facilitates parallelization, enables point-of-care use of diagnostic equipment and even reduces the amount of potentially infectious disposables, characteristics that are highly desirable in most healthcare settings. This critical review emphasizes our vision on the importance of multiparametric testing for diagnosing pneumococcal infections in patients with fever and examines recent relevant developments in micro/nanotechnologies to achieve this goal.

Artemisinins, the mainstay in the treatment of malaria today, are used in combination with other antimalarials to forestall resistance, as artemisinin-combination therapies. In line with the World Health Organization’s recommendation in that respect, solid lipid nanoparticles (SLN) were formulated to encapsulate two antimalarial drugs — artemether and lumefantrine. The nanoparticles were evaluated for size and solid state properties. Caco-2 cells were used to investigate the ability of the SLN to deliver its payload at the absorptive interface of the gastrointestinal tract. Mice heart endothelial cells (MHEC) were also used as marker cells to assess cellular uptake of coumarin 6 from the SLN with imaging by confocal laser scanning microscopy (CSLM). In vivo antimalarial activity was done using a standard suppressive protocol. The results of this study revealed different crystal properties for artemether and lumefantrine, which affected their solubility in the lipid matrix and thus, loading in the lipid nanoparticles. The particles of the SLN were within the range of 150 nm–500 nm with varied polydispersity indices. Wide angle X-ray diffraction analysis indicated the presence of particles of solid nature. Cellular uptake studies indicated uptake of coumarin 6 from the coumarin 6-labeled SLN. In vivo antimalarial studies indicated high clearance of parasitemia with minimal effect on hematological parameters tested.

Mupirocin is an antibiotic having a unique mode of action, not shared by any other therapeutically available antibiotic. However, due to its rapid elimination following injection and high protein binding, current therapeutic use is limited to topical administration. Computational methods have identified mupirocin as a good candidate for delivery via long-circulating nano-liposomes. Formulating mupirocin in such liposomes to form Nano-mupirocin protects the drug in the circulation, enabling therapeutic efficacy. This was demonstrated using two different animal models that served as a proof of concept: the mice necrotizing fasciitis and rabbit endocarditis models. In both animal models, mupirocin administered intravenously (IV) lacked therapeutic efficacy, while the Nano-mupirocin administered IV was efficacious. In both mice and rabbits the pharmacokinetic (PK) profile following IV injection of Nano-mupirocin showed significantly greater AUC and elimination half-life of Nano-mupirocin compared to the free drug. In addition, in mice we also demonstrated significant drug distribution into the disease site. These PK profiles may explain Nano-mupirocin’s superior therapeutic efficacy. To the best of our knowledge, this is the first study demonstrating that systemic activity of mupirocin is feasible. Therefore, Nano-mupirocin can be considered a novel and unique parenteral antibiotic candidate drug.

The incorporation of radioactive isotope(s) into conventional nanomaterials can bring extra properties which are not possessed by original materials. The resulting radioactive nanomaterials (radio-nanomaterials), with added physical/chemical properties, can be used as important tools for different biomedical applications. In this review, our goal is to provide an up-to-date overview on these applications using radio-nanomaterials. The first section illustrates the utilization of radio-nanomaterials for understanding of in vivo kinetics of their parent nanomaterials. In the second section, we focus on two primary applications of radio-nanomaterials: imaging and therapeutic delivery. With various methods being used to form radio-nanomaterials, they can be used for positron emission tomography (PET), single-photon emission computed tomography (SPECT), and multimodal imaging. Therapeutic isotopes-loading radio-nanomaterials can possess selective killing efficacy of diseased cells (e.g. tumor cells) and can provide promises for certain isotopes which are not able to be used in a conventional manner. The successful and versatile biomedical applications of radio-nanomaterials warrants further investigations of those materials and their optimizations can pave the way to future imaging guidable, personalized treatments in patients.