Peptides as Therapeutic Agents for Inflammatory-Related Diseases

Manna, Sara La; Natale, Concetta Di; Florio, Daniele; Marasco, Daniela

doi:10.3390/ijms19092714

Cited by 111 publications

(99 citation statements)

References 97 publications

(125 reference statements)

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“…Substantial industrial efforts were made to address the delivery of effector substances into the cell's interior, the development of small molecule inhibitors, peptides, or liposomal-based drugs. Several FDA-approved drugs in liposomal formulations are on the market for indications like infections and cancer [81,82]. A major challenge represents the import of natural or synthetic molecules of high molecular weight or genetic material due to their physicochemical properties that render them unsuitable for crossing the lipid bilayer of the plasma membranes [83,84].…”

Section: Delivery Of Substances Into the Cell's Interiormentioning

confidence: 99%

Cell-Type Targeted NF-kappaB Inhibition for the Treatment of Inflammatory Diseases

Sehnert

Burkhardt

Dübel

et al. 2020

Cells

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Deregulated NF-k activation is not only involved in cancer but also contributes to the pathogenesis of chronic inflammatory diseases like rheumatoid arthritis (RA) and multiple sclerosis (MS). Ideally, therapeutic NF-KappaB inhibition should only take place in those cell types that are involved in disease pathogenesis to maintain physiological cell functions in all other cells. In contrast, unselective NF-kappaB inhibition in all cells results in multiple adverse effects, a major hindrance in drug development. Hitherto, various substances exist to inhibit different steps of NF-kappaB signaling. However, powerful tools for cell-type specific NF-kappaB inhibition are not yet established. Here, we review the role of NF-kappaB in inflammatory diseases, current strategies for drug delivery and NF-kappaB inhibition and point out the “sneaking ligand” approach. Sneaking ligand fusion proteins (SLFPs) are recombinant proteins with modular architecture consisting of three domains. The prototype SLC1 binds specifically to the activated endothelium and blocks canonical NF-kappaB activation. In vivo, SLC1 attenuated clinical and histological signs of experimental arthritides. The SLFP architecture allows an easy exchange of binding and effector domains and represents an attractive approach to study disease-relevant biological targets in a broad range of diseases. In vivo, SLFP treatment might increase therapeutic efficacy while minimizing adverse effects.

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Section: Delivery Of Substances Into the Cell's Interiormentioning

confidence: 99%

Cell-Type Targeted NF-kappaB Inhibition for the Treatment of Inflammatory Diseases

Sehnert

Burkhardt

Dübel

et al. 2020

Cells

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“…Therefore, the experimental data were not far from the calculated ones, indicating the suitability of the non-linear first-order kinetic equation model. Release rate studies are important to control, tune and adjust the drug dose during a time-long therapy such as for diabetes [43], chemotherapy [44] and other chronic diseases as neurological [45] or inflammation diseases [46,47].To this end, mathematical modeling can provide valuable information on the mechanism of the release process [25].…”

Section: In Silico Predictionmentioning

confidence: 99%

Tunable Release of Curcumin with an In Silico-Supported Approach from Mixtures of Highly Porous PLGA Microparticles

et al. 2020

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In recent years, drug delivery systems have become some of the main topics within the biomedical field. In this scenario, polymeric microparticles (MPs) are often used as carriers to improve drug stability and drug pharmacokinetics in agreement with this kind of treatment. To avoid a mere and time-consuming empirical approach for the optimization of the pharmacokinetics of an MP-based formulation, here, we propose a simple predictive in silico-supported approach. As an example, in this study, we report the ability to predict and tune the release of curcumin (CUR), used as a model drug, from a designed combination of different poly(d,l-lactide-co-glycolide) (PLGA) MPs kinds. In detail, all CUR–PLGA MPs were synthesized by double emulsion technique and their chemical–physical properties were characterized by Mastersizer and scanning electron microscopy (SEM). Moreover, for all the MPs, CUR encapsulation efficiency and kinetic release were investigated through the UV–vis spectroscopy. This approach, based on the combination of in silico and experimental methods, could be a promising platform in several biomedical applications such as vaccinations, cancer-treatment, diabetes therapy and so on.

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“…A promising field to answer to drug resistance in the pharmaceutical research is the development of novel and peptide-based compounds as therapeutic antibiotics. Often, peptides demonstrated elected compounds to target proper and difficult targets as protein complexes for their high specificity as well as recent and innovative synthetic strategies [7]. Several natural antimicrobial peptides (AMPs) have been identified over time and many improvements of their biological activity were achieved through their ad hoc chemical modifications.…”

Section: Introductionmentioning

confidence: 99%

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

Natale

Benedictis

et al. 2020

Antibiotics

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In metal-peptide interactions, cations form stable complexes through bonds with coordinating groups as side chains of amino acids. These compounds, among other things, exert a wide variety of antimicrobial activities through structural changes of peptides upon metal binding and redox chemistry. They exhibit different mechanisms of action (MOA), including the modification of DNA/RNA, protein and cell wall synthesis, permeabilization and modulation of gradients of cellular membranes. Nowadays, the large increase in antibiotic resistance represents a crucial problem to limit progression at the pandemic level of the diseases that seemed nearly eradicated, such as tuberculosis (Tb). Mycobacterium tuberculosis (Mtb) is intrinsically resistant to many antibiotics due to chromosomal mutations which can lead to the onset of novel strains. Consequently, the maximum pharmaceutical effort should be focused on the development of new therapeutic agents and antimicrobial peptides can represent a valuable option as a copious source of potential bioactive compounds. The introduction of a metal center can improve chemical diversity and hence specificity and bioavailability while, in turn, the coordination to peptides of metal complexes can protect them and enhance their poor water solubility and air stability: the optimization of these parameters is strictly required for drug prioritization and to obtain potent inhibitors of Mtb infections with novel MOAs. Here, we present a panoramic review of the most recent findings in the field of metal complex-peptide conjugates and their delivery systems with the potential pharmaceutical application as novel antibiotics in Mtb infections.

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Peptides as Therapeutic Agents for Inflammatory-Related Diseases

Cited by 111 publications

References 97 publications

Cell-Type Targeted NF-kappaB Inhibition for the Treatment of Inflammatory Diseases

Cell-Type Targeted NF-kappaB Inhibition for the Treatment of Inflammatory Diseases

Tunable Release of Curcumin with an In Silico-Supported Approach from Mixtures of Highly Porous PLGA Microparticles

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

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