Advancing the Therapeutic Efficacy of Bioactive Molecules by Delivery Vehicle Platforms.

2020 ◽  
Vol 27 ◽  
Author(s):  
Antonis D. Tsiailanis ◽  
Andreas G. Tzakos ◽  
Thomas Mavromoustakos
Keyword(s):  
Gold Nanoparticles ◽  
Angiotensin Ii ◽  
Therapeutic Index ◽  
Bioactive Molecules ◽  
Host Molecule ◽  
Delivery Vehicle ◽  
Metabolic Products ◽  
Activity Enhancement ◽  
Technological Platforms ◽  
Low Solubility

: Drugs have to overcome numerous barriers to reach their desired therapeutic targets. In several cases drugs, especially the highly lipophilic molecules, suffer from low solubility and bioavailability and therefore their desired targeting is hampered. In addition, undesired metabolic products might be produced or off-targets could be recognized. Along these lines, nanopharmacology has provided new technological platforms, to overcome these boundaries. Specifically, numerous vehicle platforms such as cyclodextrins and calixarenes have been widely utilized to host lipophilic drugs such as antagonists of the angiotensin II AT1 receptor (AT1R), as well as quercetin and silibinin. The encapsulation of these drugs in supramolecules or other systems refines their solubility and metabolic stability, increases their selectivity and therefore decreases their effective dose and improves the therapeutic index. In this minireview we report on the formulations of Silibinin and AT1R antagonist candesartan in a 2-HP-β-cyclodextrin host molecule, which displayed enhanced cytotoxicity and increased silibinin’s and candesartan’s stability, respectively. Moreover we describe the encapsulation of quercetin in gold nanoparticles bearing a calixarene supramolecular host. Also the encapsulation of temozolomide in a calixarene nanocapsule has been described. Finally, we report on the activity enhancement that has been achieved upon using these formulations as well as the analytical and computational methods we used to characterize these formulations and explore the molecular interactions between the host and quest molecules.

Pulmonary Endothelial Cells / Metabolism of Vasoactive Substances

1975 ◽  
Author(s):  
J. W. Ryan ◽  
Una S. Ryan
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Angiotensin I ◽  
Clotting System ◽  
Arterial Circulation ◽  
Pulmonary Endothelial Cells ◽  
Vasoactive Substances ◽  
Metabolic Products ◽  
Relationship Of ◽  
The Relationship

The lungs metabolize a variety of vasoactive substances, including bradykinin (BK), angiotensin I (AT I), PGE2 and F2α, norepinephrine, 5-HT, 5’-ATP and 5’-AMP. In contrast, the lungs od not metabolize angiotensin II (AT II), PGA2, histamine and epinephrine. Of the substances metabolized, all (with the possible exceptions of the prostaglandins) are processed primarily by the pulmonary endothelial cells. Furthermore, the means by which the substances are processed suggest that endothelial cells determine the vasoactive substances allowed to enter the systemic arterial circulation. BK is inactivated while AT I is converted to its potent homolog, AT II. AT II enters the arterial circulation. The metabolism of BK and AT I may be effected by the same enzyme. Pulmonary endothelial cells are a rich source of thromboplastin, an enzyme capable of degrading BK and AT I. However, the relationship of thromboplastin to the fates of these hormones is not clear : The metabolic products produced are not those produced by intact lungs nor by endothelial cells in culture. In addition, thromboplastin degrades substances (e.g. AT II), which are not degraded by intact lungs. Possibly the extrinsic clotting system plays a role when activated but not under physiologic conditions.

scholarly journals Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1407
Author(s):  
Courtney van Ballegooie ◽  
Alice Man ◽  
Alessia Pallaoro ◽  
Marcel Bally ◽  
Byron D. Gates ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
External Beam Radiation ◽  
Therapeutic Effects ◽  
Delivery Vehicle ◽  
Triggered Release ◽  
Gold Particles ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Zein Protein

Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.

Cyclodextrin Capped Gold Nanoparticles as a Delivery Vehicle for a Prodrug of Cisplatin

2013 ◽  
Vol 52 (16) ◽  
pp. 9418-9426 ◽  
Author(s):  
Yi Shi ◽  
Jerry Goodisman ◽  
James C. Dabrowiak
Keyword(s):  
Gold Nanoparticles ◽  
Delivery Vehicle

scholarly journals Natural Products to Fight Cancer: A Focus on Juglans regia

Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 469 ◽  
Author(s):  
Elena Catanzaro ◽  
Giulia Greco ◽  
Lucia Potenza ◽  
Cinzia Calcabrini ◽  
Carmela Fimognari
Keyword(s):  
Natural Products ◽  
Essential Fatty Acids ◽  
Juglans Regia ◽  
Therapeutic Index ◽  
Natural World ◽  
Bioactive Molecules ◽  
Human Society ◽  
Beneficial Effects ◽  
Anticancer Effects ◽  
Pharmacologic Activity

Even if cancer represents a burden for human society, an exhaustive cure has not been discovered yet. Low therapeutic index and resistance to pharmacotherapy are two of the major limits of antitumour treatments. Natural products represent an excellent library of bioactive molecules. Thus, tapping into the natural world may prove useful in identifying new therapeutic options with favourable pharmaco-toxicological profiles. Juglans regia, or common walnut, is a very resilient tree that has inhabited our planet for thousands of years. Many studies correlate walnut consumption to beneficial effects towards several chronic diseases, such as cancer, mainly due to the bioactive molecules stored in different parts of the plant. Among others, polyphenols, quinones, proteins, and essential fatty acids contribute to its pharmacologic activity. The present review aims to offer a comprehensive perspective about the antitumour potential of the most promising compounds stored in this plant, such as juglanin, juglone, and the ellagitannin-metabolites urolithins or deriving from walnut dietary intake. All molecules and a chronic intake of the fruit provide tangible anticancer effects. However, the scarcity of studies on humans does not allow results to be conclusive.

scholarly journals Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

Materials ◽  
2020 ◽  
Vol 13 (3) ◽  
pp. 570 ◽  
Author(s):  
Claudia Sandoval-Yañez ◽  
Cristian Castro Rodriguez
Keyword(s):  
Drug Delivery Systems ◽  
Structural Modification ◽  
Physicochemical Characteristics ◽  
Therapeutic Strategies ◽  
Delivery Systems ◽  
Bioactive Molecules ◽  
Target Tissue ◽  
Bioactive Molecule ◽  
Low Solubility ◽  
Low Solubility Drugs

Today, dendrimers are the main nanoparticle applied to drug delivery systems. The physicochemical characteristics of dendrimers and their versatility structural modification make them attractive to applied as a platform to bioactive molecules transport. Nanoformulations based on dendrimers enhance low solubility drugs, arrival to the target tissue, drugs bioavailability, and controlled release. This review describes the latter approaches on the transport of bioactive molecules based on dendrimers. The review focus is on the last therapeutic strategies addressed by dendrimers conjugated with bioactive molecules. A brief review of the latest studies in therapies against cancer and cardiovascular diseases, as well as future projections in the area, are addressed.

scholarly journals The Triprenylated Anthranoid Ferruginin A, a Promising Scaffold for the Development of Novel Antibiotics against Gram-Positive Bacteria

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 84
Author(s):  
Bruno Casciaro ◽  
Francesca Ghirga ◽  
Floriana Cappiello ◽  
Valeria Vergine ◽  
Maria Rosa Loffredo ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Therapeutic Index ◽  
Human Keratinocytes ◽  
Bioactive Molecules ◽  
Primary Sources ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Substructure Search ◽  
Gram Positive Bacteria ◽  
Further Development

In today’s post-antibiotic era, the search for new antimicrobial compounds is of major importance and nature represents one of the primary sources of bioactive molecules. In this work, through a cheminformatics approach, we clustered an in-house library of natural products and their derivatives based on a combination of fingerprints and substructure search. We identified the prenylated emodine-type anthranoid ferruginin A as a novel antimicrobial compound. We tested its ability to inhibit and kill a panel of Gram-positive and Gram-negative bacteria, and compared its activity with that of two analogues, vismione B and ferruanthrone. Furthermore, the capability of these three anthranoids to disrupt staphylococcal biofilm was investigated, as well as their effect on the viability of human keratinocytes. Ferruginin A showed a potent activity against both the planktonic and biofilm forms of Gram-positive bacteria (i.e., Staphylococcus aureus and S. epidermidis) and had the best therapeutic index compared to vismione B and ferruanthrone. In conclusion, ferruginin A represents a promising scaffold for the further development of valuable antimicrobial agents.

scholarly journals Preparing the Bone Tissue Regeneration Ground by Exosomes: From Diagnosis to Therapy

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4205
Author(s):  
Batla Al-Sowayan ◽  
Farah Alammari ◽  
Alaa Alshareeda
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Extracellular Vesicle ◽  
Bioactive Molecules ◽  
Bone Tissue Regeneration ◽  
Paracrine Factor ◽  
Delivery Vehicle ◽  
Immune Modulators ◽  
Clinical Utilization

Bone tissue engineering employs acellular scaffolds or scaffolds, along with cells and growth factors, to provide the mechanical support needed, as well as serve as a delivery vehicle for bioactive molecules to the injury sites. As tissue engineering continues to evolve, it has integrated two emerging fields: stem cells and nanotechnology. A paracrine factor that is found to be responsible for the major regenerative effect in stem cell transplantation is an extracellular vesicle called an ‘exosome’. Recent advances in nanotechnology have allowed the ‘exosome’ to be distinguished from other extracellular vesicles and be polymerized into a well-defined concept. Scientists are now investigating exosome uses in clinical applications. For bone-related diseases, exosomes are being explored as biomarkers for different bone pathologies. They are also being explored as a therapeutic agent where progenitor cell-derived exosomes are used to regenerate damaged bone tissue. In addition, exosomes are being tested as immune modulators for bone tissue inflammation, and finally as a delivery vehicle for therapeutic agents. This review discusses recently published literature on the clinical utilization of exosomes in bone-related applications and the correlated advantages. A particular focus will be placed on the potential utilization of regenerative cell-derived exosomes as a natural biomaterial for tissue regeneration.

Light-responsible DNA hydrogel–gold nanoparticle assembly for synergistic cancer therapy

2015 ◽  
Vol 3 (8) ◽  
pp. 1537-1543 ◽  
Author(s):  
Jaejung Song ◽  
Sekyu Hwang ◽  
Kyuhyun Im ◽  
Jaehyun Hur ◽  
Jutaek Nam ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Cancer Therapy ◽  
Gold Nanoparticle ◽  
Nanoparticle Assembly ◽  
Delivery Vehicle ◽  
Combination Cancer Therapy ◽  
Synergistic Combination ◽  
Dna Hydrogel

A DNA hydrogel based delivery vehicle that combines assembled gold nanoparticles and Doxorubicins showed light-triggered and synergistic combination cancer therapy at the in vitro and in vivo levels.

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