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Cancers are increasing in prevalence and many challenges remain for their treatment, such as chemoresistance and toxicity. In this context, siRNA-based therapeutics have many potential advantages for cancer therapies as a result of their ability to reduce or prevent expression of specific cancer-related genes. However, the direct delivery of naked siRNA is hindered by issues like enzymatic degradation, insufficient cellular uptake, and poor pharmacokinetics. Hence, the discovery of a safe and efficient delivery vehicle is essential. This review explores various lipid and polymer-based delivery systems for siRNA in cancer treatment. Both polymers and lipids have garnered considerable attention as carriers for siRNA delivery. While all of these systems protect siRNA and enhance transfection efficacy, each exhibits its unique strengths. Lipid-based delivery systems, for instance, demonstrate high entrapment efficacy and utilize cost-effective materials. Conversely, polymeric-based delivery systems offer advantages through chemical modifications. Nonetheless, certain drawbacks still limit their usage. To address these limitations, combining different materials in formulations (lipid, polymer, or targeting agent) could enhance pharmaceutical properties, boost transfection efficacy, and reduce side effects. Furthermore, co-delivery of siRNA with other therapeutic agents presents a promising strategy to overcome cancer resistance. Lipid-based delivery systems have been demonstrated to encapsulate many therapeutic agents and with high efficiency, but most are limited in terms of the functionalities they display. In contrast, polymeric-based delivery systems can be chemically modified by a wide variety of routes to include multiple components, such as release or targeting elements, from the same materials backbone. Accordingly, by incorporating multiple materials such as lipids, polymers, and/or targeting agents in RNA formulations it is possible to improve the pharmaceutical properties and therapeutic efficacy while reducing side effects. This review focuses on strategies to improve siRNA cancer treatments and discusses future prospects in this important field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

In pharmaceutical technology, lipids and polymers are considered pillar excipients for the fabrication of most dosage forms, irrespective of the administration route. They play various roles ranging from support vehicles to release rate modifiers, stabilizers, solubilizers, permeation enhancers and transfection agents. Focusing on selected applications, which were discussed at the Annual Scientific Meeting of the Gattefossé Foundation 2018, this manuscript recapitulates the fundamental roles of these two important classes of excipients, either employed alone or in combination, and provides insight on their functional properties in various types of drug formulations. Emphasis is placed on oral formulations for the administration of active pharmaceutical ingredients with low aqueous solubilities or poor permeation properties. Additionally, this review article covers the use of lipids and polymers in the design of colloidal injectable delivery systems, and as substrates in additive manufacturing technologies for the production of tailor-made dosage forms., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Nowadays, the interest in research towards the local administration of drugs via the inhalation route is growing as it enables the direct targeting of the lung tissue, at the same time reducing systemic side effects. This is of great significance in the era of nucleic acid therapeutics and personalized medicine for the local treatment of severe lung diseases. However, the success of any inhalation therapy is driven by a delicate interplay of factors, such as the physiochemical profile of the payload, formulation, inhalation device, aerodynamic properties, and interaction with the lung fluids. The development of drug delivery systems tailored to the needs of this administration route is central to its success and to revolutionize the treatment of respiratory diseases. With this review, we aim to provide an up-to-date overview of advances in the development of nanoparticulate carriers for drug delivery to the lung tissue, with special regard concerning lipid and polymer-based nanocarriers (NCs). Starting from the biological barriers that the anatomical structure of the lung imposes, and that need to be overcome, the current strategies to achieve efficient lung delivery and the best support for the success of NCs for inhalation are highlighted. [ABSTRACT FROM AUTHOR]

Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano‐delivery system for therapeutic nucleic acids. The great effort put in the development of ionizable lipids with increased in vivo potency brought LNPs from the laboratory benches to the FDA approval of patisiran in 2018 and the ongoing clinical trials for mRNA‐based vaccines against SARS‐CoV‐2. Despite these success stories, several challenges remain in RNA delivery, including what is known as "endosomal escape." Reaching the cytosol is mandatory for unleashing the therapeutic activity of RNA molecules, as their accumulation in other intracellular compartments would simply result in efficacy loss. In LNPs, the ability of ionizable lipids to form destabilizing non‐bilayer structures at acidic pH is recognized as the key for endosomal escape and RNA cytosolic delivery. This is motivating a surge in studies aiming at designing novel ionizable lipids with improved biodegradation and safety profiles. In this work, we describe the journey of RNA‐loaded LNPs across multiple intracellular barriers, from the extracellular space to the cytosol. In silico molecular dynamics modeling, in vitro high‐resolution microscopy analyses, and in vivo imaging data are systematically reviewed to distill out the regulating mechanisms underlying the endosomal escape of RNA. Finally, a comparison with strategies employed by enveloped viruses to deliver their genetic material into cells is also presented. The combination of a multidisciplinary analytical toolkit for endosomal escape quantification and a nature‐inspired design could foster the development of future LNPs with improved cytosolic delivery of nucleic acids. [ABSTRACT FROM AUTHOR]