Abstract
The use of pharmacologically active compounds to manage and treat diseases is of utmost relevance in clinical practice. It is well recognized that spatial-temporal control over the delivery of these biomolecules will greatly impact their pharmacokinetic profile and ultimately their therapeutic effect. Nanoparticles (NPs) prepared from different materials have been tested successfully in the clinic for the delivery of several biomolecules including non-coding RNAs (siRNA and miRNA) and mRNAs. Indeed, the recent success of mRNA vaccines is in part due to progress in the delivery systems (NP based) that have been developed for many years. In most cases, the identification of the best formulation was done by testing a small number of novel formulations or by modification of pre-existing ones. Unfortunately, this is a low throughput and time-consuming process that hinders the identification of formulations with the highest potential. Alternatively, high-throughput combinatorial design of NP libraries may allow the rapid identification of formulations with the required release and cell/tissue targeting profile for a given application. Combinatorial approaches offer several advantages over conventional methods since they allow the incorporation of multiple components with varied chemical properties into materials, such as polymers or lipid-like materials, that will subsequently form NPs by self-assembly or chemical conjugation processes. The current review highlights the impact of high-throughput in the development of more efficient drug delivery systems with enhanced targeting and release kinetics. It also describes the current challenges in this research area as well as future directions.
Highlights
INTRODUCTIONThe use of nanotechnologies for the prevention, diagnosis, and treatment of diseases in medicine can have a major impact on human health
The recent success of mRNA vaccines is in part due to progress in the delivery systems (NP based) that have been developed for many years
In 2016, there were 25 Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved nanomedicines, and more than 45 NP formulations that were under evaluation in clinical trials.[3]
Summary
The use of nanotechnologies for the prevention, diagnosis, and treatment of diseases in medicine can have a major impact on human health. NPs are used to (i) increase therapeutic efficacy, (ii) decrease the therapeutically effective dose, and/or (iii) reduce the risk of systemic side effects; and these can be achieved by improving the solubility, by controlling the passive and/or active targeting, or by endogenously and/or exogenously triggering release of the payload.[1,2] Despite their therapeutic advantages and the promising results obtained in preclinical studies, the number of NP-based products used in the clinic is still limited. This review discusses the current challenges and future directions of high-throughput screening for the development of more efficient drug delivery systems, in the context of non-coding RNAs and mRNAs. Initially, we cover historic facts about HTS, how/when the HTS was applied to the area of drug delivery, preparation of NP libraries, and the impact of HTS approaches in medicine. We discuss how this research area might advance in the near future and the expected impact
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