The rational design of drug delivery approaches leveraging supramolecular chemistry (
i.e.
, "
chemistry beyond the molecule
") has garnered significant interest in recent years toward improving ...therapeutics. By using specific, dynamic, and tunable non-covalent interactions, engineered approaches to drug delivery can be realized. Certain benefits to this approach are molecular-level control of composition, improved routes for incorporating and targeting drugs, and new strategies to create delivery devices that respond to a variety of physiologic indicators. Some of the most recognizable supramolecular motifs - macrocyclic host-guest complexes - afford logical application to drug delivery in using drug as guest. The use of supramolecular motifs may further give rise to materials for the controlled encapsulation and release of therapeutics. Furthermore, given the majority of supramolecular motifs in water are directed by hydrophobic interactions, cooperative delivery strategies can be realized. The modularity of supramolecular interactions also facilitates opportunities to combine multiple drugs within one delivery platform, as well as the facile incorporation of targeting units. In sum, supramolecular design offers ample opportunity to improve the precision of pharmaceutical practice. In the context of clinical translation, features of supramolecular design may prove additionally advantageous, specifically in enabling quantitative drug loading, molecularly discrete delivery devices, and
a priori
knowledge of carrier degradation and clearance mechanisms. As such, the design opportunities afforded by supramolecular chemistry will play a vital role in the future of the drug delivery field.
Principles rooted in supramolecular chemistry have empowered new and highly functional therapeutics and drug delivery devices. This general approach offers elegant tools rooted in molecular and materials engineered to address the many challenges faced in treating disease.
In 2014, the American Diabetes Association instituted a novel funding paradigm to support diabetes research through its Pathway to Stop Diabetes® Program. Pathway took a multifaceted approach to ...provide key funding to diabetes researchers in advancing a broad spectrum of research programs centered on all aspects of understanding, managing, and treating diabetes. Herein the personal perspective of a 2019 Pathway Accelerator awardee is offered, describing a research program seeking to advance a materials-centered approach to engineering glucose-responsive devices and new delivery tools for better therapeutic outcomes in treating diabetes. This is offered alongside a personal reflection on five years of support from the ADA Pathway Program.
In 2014, the American Diabetes Association instituted a novel funding paradigm to support diabetes research through its Pathway to Stop Diabetes® Program. Pathway took a multifaceted approach to ...provide key funding to diabetes researchers in advancing a broad spectrum of research programs centered on all aspects of understanding, managing, and treating diabetes. Herein the personal perspective of a 2019 Pathway Accelerator awardee is offered, describing a research program seeking to advance a materials-centered approach to engineering glucose-responsive devices and new delivery tools for better therapeutic outcomes in treating diabetes. This is offered alongside a personal reflection on five years of support from the ADA Pathway Program.
Though therapeutics based on messenger RNA (mRNA) have broad potential in applications such as protein replacement therapy, cancer immunotherapy, and genomic engineering, their effective ...intracellular delivery remains a challenge. A chemically diverse suite of delivery materials with origins as materials for cellular transfection of DNA and small interfering RNAs (siRNAs) has recently been reported to have promise as non-viral delivery agents for mRNA. These materials include covalent conjugates, protamine complexes, nanoparticles based on lipids or polymers, and hybrid formulations. This review will highlight the use of delivery materials for mRNA, with a specific focus on their mechanisms of action, routes of administration, and dosages. Additionally, strategies in which these materials can be adapted and optimized to address challenges specific to mRNA delivery are also discussed. The technologies included have shown varying promise for therapeutic use, specifically having been used to deliver mRNA in vivo or exhibiting characteristics that could make in vivo use a possibility. In so doing, it is the intention of this review to provide a comprehensive look at the progress and possibilities in applying nucleic acid delivery technology specifically toward the emerging area of mRNA therapeutics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
5.
Drug Delivery with Designed Peptide Assemblies Sis, Matthew J.; Webber, Matthew J.
Trends in pharmacological sciences (Regular ed.),
October 2019, 2019-10-00, 20191001, Volume:
40, Issue:
10
Journal Article
Peer reviewed
Self-assembly of designed synthetic peptides is a versatile strategy to generate functional materials for many applications. Given the biological relevance of their amino acid composition, one ...logical application for this class of materials lies in drug and therapeutic delivery. Peptide design alters the ultimate device form factor, ranging from circulating nanostructures to locally applied hydrogel depots. This growing field has progressed recently from methods for the simple solubilization of hydrophobic drugs to ‘smart’ carriers that deploy drug in response to a disease biomarker. The drug itself may act as a functional driver directing the assembly of a conjugated peptide. Furthermore, the peptide may itself have properties of a drug, both through presented bioactivity and by drug-like function of assemblies interfacing with cells or tissues. Given the exciting advances in the use of peptide assemblies for drug delivery, this review outlines different peptide self-assembly designs, highlights the advantages of using peptide self-assembly in the delivery of various classes of therapeutics, and demonstrates how advanced functionalities such as targeting and disease responsiveness can be built into designed peptide systems. Additionally, we provide commentary on the opportunities and challenges ahead in this growing field.
Peptide self-assembly affords a variety of molecular-scale motifs, which enables the form factor of carriers for drug delivery to be tuned across length scales.The nanoscale carriers and network materials that result from peptide self-assembly have been used in the delivery of a wide range of therapeutic cargos from small-molecule drugs to genetic material to protein therapeutics.The peptide composition of these materials enables integration with biological mechanisms for therapeutic targeting as well as enhanced specificity through stimulus-responsive functionality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
6.
Less is more when forming gels by dilution Webber, Matthew J
Science (American Association for the Advancement of Science),
07/2022, Volume:
377, Issue:
6602
Journal Article
Peer reviewed
Molecular self-assembly yields soft materials arising from the liquid state when diluted.
Slow, tunable dissociation of non-covalent host–guest complexes confers supramolecular polymer networks with excellent compressive strength and self-recovery.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
8.
Supramolecular biomaterials Webber, Matthew J; Appel, Eric A; Meijer, E W ...
Nature materials,
01/2016, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Polymers, ceramics and metals have historically dominated the application of materials in medicine. Yet rationally designed materials that exploit specific, directional, tunable and reversible ...non-covalent interactions offer unprecedented advantages: they enable modular and generalizable platforms with tunable mechanical, chemical and biological properties. Indeed, the reversible nature of supramolecular interactions gives rise to biomaterials that can sense and respond to physiological cues, or that mimic the structural and functional aspects of biological signalling. In this Review, we discuss the properties of several supramolecular biomaterials, as well as their applications in drug delivery, tissue engineering, regenerative medicine and immunology. We envision that supramolecular biomaterials will contribute to the development of new therapies that combine highly functional materials with unmatched patient- and application-specific tailoring of both material and biological properties.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
9.
Temperature-responsive supramolecular hydrogels Xian, Sijie; Webber, Matthew J
Journal of materials chemistry. B, Materials for biology and medicine,
10/2020, Volume:
8, Issue:
4
Journal Article
Peer reviewed
Hydrogels comprise a class of soft materials which are extremely useful in a number of contexts, for example as matrix-mimetic biomaterials for applications in regenerative medicine and drug ...delivery. One particular subclass of hydrogels consists of materials prepared through non-covalent physical crosslinking afforded by supramolecular recognition motifs. The dynamic, reversible, and equilibrium-governed features of these molecular-scale motifs often transcend length-scales to endow the resulting hydrogels with these same properties on the bulk scale. In efforts to engineer hydrogels of all types with more precise or application-specific uses, inclusion of stimuli-responsive sol-gel transformations has been broadly explored. In the context of biomedical uses, temperature is an interesting stimulus which has been the focus of numerous hydrogel designs, supramolecular or otherwise. Most supramolecular motifs are inherently temperature-sensitive, with elevated temperatures commonly disfavoring motif formation and/or accelerating its dissociation. In addition, supramolecular motifs have also been incorporated for physical crosslinking in conjunction with polymeric or macromeric building blocks which themselves exhibit temperature-responsive changes to their properties. Through molecular-scale engineering of supramolecular recognition, and selection of a particular motif or polymeric/macromeric backbone, it is thus possible to devise a number of supramolecular hydrogel materials to empower a variety of future biomedical applications.
A subclass of hydrogels which are prepared from supramolecular interactions can realized enhanced functionality, especially in the context of biomedical applications, upon the inclusion of temperature-responsive properties.
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