Transformative Materials for Interfacial Drug Delivery
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Abstract
Drug delivery systems (DDS) are designed to temporally and spatially control drug availability and activity. They assist in improving the balance between on-target therapeutic efficacy and off-target toxic side effects. DDS aid in overcoming biological barriers encountered by drug molecules upon applying them via various routes of administration. They are furthermore increasingly explored for modulating the interface between implanted (bio)medical materials and host tissue. Here, an overview of the biological barriers and host-material interfaces encountered by DDS upon oral, intravenous, and local administration is provided, and material engineering advances at different time and space scales to exemplify how current and future DDS can contribute to improved disease treatment are highlighted.
Introduction
Drug delivery systems (DDS) aim to improve therapeutic efficacy and reduce side effects. DDS offers several advantages over conventional free drug formulations. They can, for instance, protect unstable drugs, or aid in increasing the aqueous solubility of highly hydrophobic drugs. They furthermore help to control drug distribution and activation, thereby improving the pharmacokinetics and target site accumulation of small molecules.[1-3] Traditional examples in this regard are coated tablets or capsules that protect drugs from low pH or digestive enzymes in the stomach, or pegylated nanoparticles (NP) that are routinely used to encapsulate small molecule chemotherapeutics to increase their circulation half-life and tumor accumulation. DDS can be sub-categorized into systems that assist in better controlling the temporal aspects of drug activation and systems that help to spatially guide drug molecules to certain organs or pathological sites within the body (Figure 1).
Depending on the route of administration, drugs and DDS encounter multiple biological barriers. Oral delivery is, for example, hampered by the harsh acidic conditions in the stomach and by poor permeability across the intestinal epithelium. Upon intravenous (IV) delivery, nano- and micro-DDS delivery suffer from rapid clearance by the mononuclear phagocyte system, as well as from the structural integrity of vascular endothelium. For local administration, the presence of mucus, for example, in the airways and the vaginal tract, can lead to inefficient drug delivery. These and other biological barriers impede DDS performance and therapeutic efficacy.[4-7] Other than biological barriers, patient adherence to medication is often an overlooked barrier, which must be taken into consideration while designing DDS. Different approaches to overcome this barrier are highlighted in detail by Baryakova et al.[8]
To promote drug delivery across biological barriers, it is important to look at barriers not as hurdles, but as targetable, interactive, and adaptive interfaces. Interfacial drug delivery can be achieved in various different ways, and upon different routes of application (as well as via DDS integration in implants), with the overarching goal of temporally and spatially enhancing drug delivery and drug activity.[9-11] Novel materials and methods for interface modulation open up new directions for transformative DDS development and improved DDS performance.[12]
In this perspective, we discuss the biological barriers and in vivo interfaces that DDS encounter upon oral, IV, and local administration. We furthermore highlight recent advances in DDS engineering and bio-material interface modulation, which are together resulting in radical improvements in temporally and spatially targeted drug treatment.
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Prachi Desai, Anshuman Dasgupta, Alexandros Marios Sofias, Quim Peña, Robert Göstl, Ioana Slabu, Ulrich Schwaneberg, Thomas Stiehl, Wolfgang Wagner, Stefan Jockenhövel, Julia Stingl, Rafael Kramann, Christian Trautwein, Tim H. Brümmendorf, Fabian Kiessling, Andreas Herrmann, and Twan Lammers, Transformative Materials for Interfacial Drug Delivery, Adv. Healthcare Mater. 2023, 2301062, © 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH, DOI: 10.1002/adhm.202301062
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