DRUG PROFILES

Qinghaosu

To ensure the safety of drugs in clinical use and avoid side effects, the impurity content should be strictly controlled. Artemisitene (ARE) has quite similar structure to that of the antimalarial artemisinin, and thus is difficult to be removed from the target drug. The traditional column chromatography method to purify artemisinin has low separation efficiency and needs lots of organic solvents. In this work, functional ionic liquid (IL), 1-(trimethoxysilyl) benzene-3-vinylimidazolium chloride, modified silica materials were synthesized. Composition of the functional materials were characterized by energy dispersive spectroscopy, FT-IR, and X-ray photoelectron spectroscopy. It was indicated that the designed ionic liquid was successfully grafted onto SiO₂. Adsorption capacity of the prepared ionic liquid-based material for artemisinin and artemisitene was evaluated, and it was demonstrated that adsorption of ARE by the functional material was a quick process, and the adsorption kinetics followed the Elovich Model. This kind of IL@SiO₂ material exhibited excellent performance in selective separation of artemisitene from artemisinin. Mechanism exploration by spectroscopic analysis revealed that π-π conjugated interactions between the unsaturated bond (the C=C bond and aromatic ring) in the ionic liquid and artemisitene enhanced the molecular recognition capability of IL@SiO₂ for ARE, resulting in selective separation of these two structurally analogues.

Traditional treatments for human papillomavirus-related cutaneous diseases include 5-aminolevulinic acid photodynamic therapy, cryotherapy, microwave ablation, and surgical resection. These treatment methods involvevarious adverse reactions; therefore, it remains necessary to explore new treatment methods. Dihydroartemisinin shows cytotoxic effects against several malignancies by producing reactive oxygen species, and heme environments reportedly enhance its activity. However, the underlying mechanismsare still unclear. Therefore, we investigated the mechanism of dihydroartemisininin inhuman papillomavirus-infected cells.

HeLa cells were treated with dihydroartemisinin, 5-aminolevulinic acid, and succinylacetone. The cell viability, apoptosis, mitochondrial membrane potential, and reactive oxygen species levels were investigated, and via western blotting analysis and polymerase chain reaction, dihydroartemisinin activity-related pathways were also determined.

Dihydroartemisinin inhibited HeLa cell proliferation and promoted cell apoptosis via the Bax/Bcl-2-Caspase pathway in a concentration-dependent manner. The specific cytotoxicity toward HeLa cells was enhanced by the addition of 5-aminolevulinic acid, a clinically used heme-synthesis precursor, owing to an increase in heme levels. Conversely, following the addition of succinylacetone, a heme synthesis blocker, heme levels decreased. Furthermore, dihydroartemisinin significantly increased reactive oxygen species levels as intracellular heme synthesis increased. Moreover, photodynamic therapy following dihydroartemisinin and 5-aminolevulinic acid treatment further enhanced the cytotoxic effect of dihydroartemisinin on high-risk human papillomavirus-infected cells.

Dihydroartemisinin exerts acytotoxic effect on high-risk human papillomavirus-infected cells by modulating heme levels via the Bax/Bcl–2-Caspase pathway, and the dihydroartemisinin, 5-aminolevulinic acid, photodynamic therapy combination treatment significantly enhanced its cytotoxic effect on human papillomavirus-infected cells.

In the early 2000s, artemisinin-based combination therapy (ACT) was introduced as first-line treatment for uncomplicated Plasmodium falciparum malaria in virtually all endemic countries. However, despite the well-known excellent tolerability of ACTs, hypersensitivity to artemisinin derivatives remains a repeatedly documented adverse drug reaction of still unknown frequency. The clinical features of an artemisinin-induced hypersensitivity reaction range from mild to life-threatening severity, and a significant number of cases may pass unnoticed. In this review, we discuss the medical importance of hypersensitivity to artemisinin derivatives and we review data on the presumed frequency and its potential underlying mechanisms. Furthermore, we advocate to make alternative non-artemisinin-based drugs available for patients who do not tolerate artemisinin derivatives and to continue investing in the development of novel non-artemisinin-based combination regimens.

Though traditional medicines have been developed through practice for thousands of years, limited research has discussed the research and development (R&D) pattern of traditional medicines. China's discovery of artemisinin accumulated valuable experiences to explore traditional medicine under low-resource settings. With limited R&D resources, China mobilized all domestic research units at different levels and departments to develop artemisinin collaboratively. The discovery of artemisinin not only based on valuable experiential wisdom of traditional medicine, but also relied on excellent synergy among all units. In this study, we reviewed the story of how artemisinin was discovered in China, summarized key factors for new drug development from traditional medicines under limited resources, and raised suggestions to utilize traditional medicines in low- and middle-income countries. This case suggested that the vitality of traditional medicine could be extended by promoting new drug development based on modern methods and collaboration.

Dihydroartemisinin (DHA) has shown cytotoxicity against various tumor cells in vitro in an iron-dependent manner, but its in vivo antitumor efficacy is compromised by its rapid degradation and clearance. Here we show the induction of ferroptosis by DHA in an immunogenic fashion and the maximization of in vivo antitumor efficacy of DHA by co-delivering a cholesterol derivative of DHA (Chol-DHA) and Pyropheophorbide-iron (Pyro-Fe) in ZnP@DHA/Pyro-Fe core-shell nanoparticles. ZnP@DHA/Pyro-Fe particles stabilize DHA against hydrolysis and prolong blood circulation of Chol-DHA and Pyro-Fe for their enhanced uptake in tumors. Co-delivery of an exogenous iron complex and DHA induces more ROS production and causes significant tumor inhibition in vivo. By increasing tumor immunogenicity, the combination of DHA and Pyro-Fe sensitizes non-immunogenic colorectal tumors to anti-PD-L1 checkpoint blockade immunotherapy. These findings suggest the potential of using nanotechnology to repurpose DHA and other drugs with excellent safety profiles for combination with immune checkpoint blockade to treat cancers.

Transition studies have started to focus on market formation in innovation systems. This article investigates market formation in a global health transition that was instigated by drug-resistant malaria. We explore how markets for Artemisinin-based Combination Therapies (ACT) in the Greater Mekong Subregion (GMS) were formed at multiple geographical scales and locations. The study reveals the role of public institutes, academia and partnerships in early innovation system development. It demonstrates how transnational organizations created a supportive global landscape for ACT development and deployment. It then reveals how these advancements led to the formation of public-sector and private-sector ACT markets in the GMS. We illustrate how market formation activities took place on global, national and local scales and how structural couplings enabled the functioning of this global innovation system. The lessons learned are particularly relevant now that drug-resistant malaria has once more emerged in the GMS, urgently calling for new therapies and associated end-user markets.