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Pharmaceuticals
Special Issues
Molecular Systems for the Delivery of Drugs and Contrast Agents
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Special Issue "Molecular Systems for the Delivery of Drugs and Contrast Agents"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 25 February 2024 | Viewed by 4624

Special Issue Editors

Dr. Luca Nardo

E-Mail Website
Guest Editor
Department of Science and High Technology, Università degli Studi dell’Insubria, Via Valleggio, 11-22100 Como (CO), Italy
Interests: advanced fluorescence spectroscopy techniques; molecular biophysics; spectroscopic evaluation and optimization of drugs and drug delivery systems; photosensitizers; amyloid aggregation; new materials; polymeric metal-organic compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Angelo Maspero

E-Mail Website
Guest Editor
Department of Science and High Technology, Università degli Studi dell’Insubria, Via Valleggio, 9, 22100 Como, CO, Italy
Interests: coordination and organometallic chemistry; homogeneous catalysis; new inorganic materials; metal–organic frameworks (MOF)
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Mauro Fasano

E-Mail Website
Guest Editor
Department of Science and High Technology, Università degli Studi dell’Insubria, Via Valleggio, 9, 22100 Como, CO, Italy
Interests: characterization of the allosteric properties of human serum albumin; biochemistry of metabolic stress pathways in neurodegenerative diseases; NMR relaxometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Effective and target-specific delivery of drugs within the organism is one of the new frontiers of pharmaceutical research and promises to enhance the in vivo safety and efficacy of virtually any candidate pharmaceutical active principle by improving their bioavailability while drastically reducing both systemic and local side effects through substantial reduction in both doses and non-specific interactions with tissues. Similar considerations apply to compounds applied for diagnostic purposes, spanning from antigens to contrast agents for diagnostic tissue imaging.

The problem is being addressed by a wealth of diverse strategies. Drug delivery systems have developed in recent decades from initial cage-like shuttles capable of incorporating the drug, thereby improving its solubility in physiological media, and gradually releasing it in time (e.g., cyclodextrines, fullerenes, plain liposomes), to expressly designed shuttles endowed with increasingly complex systems for controlled drug release, specific targeting of pathological hallmarks, or both. In parallel, the design of molecular and supramolecular structures encompassing moieties capable of targeting specific disease biomarkers and/or to promote intracellular uptake fused to the actual pharmaceutically active compound has flourished.

This Special Issue of Pharmaceutics aims to be a showcase for (supra)molecular systems or shuttles of any kind devised for the smart delivery of molecules to biological tissues for either diagnostic or therapeutic purposes. Obviously having no ambition to constitute an exhaustive panorama of the state of art in the field, we rather intend to provide an interdisciplinary forum for the reference community, with the hope to offer less sectorial points of view and, possibly, occasions to develop new networks. Accordingly, high-quality research articles in a wealth of topics including, but not limited to, biomarker- or biostructure- targeted pharmaceuticals, liposomes, phytosomes, micelles and other lipid-based nanoparticles, photo-switched drug compounds and systems for controlled release of drugs, aptameric systems for disease hallmark recognition, DNA-origami-based drug shuttles, and metal and metal–organic nanoparticles of medicinal relevance are welcomed, provided their originality and technical soundness. Well-documented reviews are also solicited, as they will help potential readers to orient within this astonishingly heterogeneous universe.

You may submit your manuscript until 30th April 2023. Contributors are encouraged to send a tentative title and/or short abstract.

Dr. Luca Nardo
Dr. Angelo Maspero
Prof. Dr. Mauro Fasano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomarker-targeted drugs
  • contrast media for diagnostic imaging
  • drug delivery systems
  • photoactivated drugs and photoswitches
  • theranostics
  • liposomes
  • biomaterials-based drugs and drug shuttles (e.g., DNA origami)
  • biomimetic materials
  • nanoparticle applications to diagnostics and therapy
  • in silico drug design

Published Papers (5 papers)

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Research

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12 pages, 2113 KiB  
Article
Molecular Resonance Imaging of the CAIX Expression in Mouse Mammary Adenocarcinoma Cells
by
Claudia Quattrociocchi
,
Alberto Mangia
,
Silvio Aime
,
Valeria Menchise
and
Daniela Delli Castelli
Pharmaceuticals 2023, 16(9), 1301; https://doi.org/10.3390/ph16091301 - 14 Sep 2023
Viewed by 431
Abstract
The carbonic anhydrase isoform IX (hCAIX) is one of the main players in extracellular tumor pH regulation, and it is known to be overexpressed in breast cancer and other common tumors. hCA IX supports the growth and survival of tumor cells, and its [...] Read more.
The carbonic anhydrase isoform IX (hCAIX) is one of the main players in extracellular tumor pH regulation, and it is known to be overexpressed in breast cancer and other common tumors. hCA IX supports the growth and survival of tumor cells, and its expression is correlated with metastasis and resistance to therapies, making it an interesting biomarker for diagnosis and therapy. The aim of this work deals with the development of an MRI imaging probe able to target the extracellular non-catalytic proteoglycan-like (PG) domain of CAIX. For this purpose, a specific nanoprobe, LIP_PepC, was designed by conjugating a peptidic interactor of the PG domain on the surface of a liposome loaded with Gd-bearing contrast agents. A Mouse Mammary Adenocarcinoma Cell Line (TS/A) was chosen as an in vitro breast cancer model to test the developed probe. MRI results showed a high selectivity and sensitivity of the imaging probe toward hCAI-expressing TS/A cells. This approach appears highly promising for the in vivo translation of a diagnostic procedure based on the targeting of hCA IX enzyme expression. Full article
(This article belongs to the Special Issue Molecular Systems for the Delivery of Drugs and Contrast Agents)
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15 pages, 3410 KiB  
Article
Physically Crosslinked Chondroitin Sulfate (CS)–Metal Ion (M: Fe(III), Gd(III), Zn(II), and Cu(II)) Particles for Versatile Applications and Their Biosafety
by
Selin S. Suner
,
Mehtap Sahiner
,
Evrim Umut
,
Ramesh S. Ayyala
and
Nurettin Sahiner
Pharmaceuticals 2023, 16(4), 483; https://doi.org/10.3390/ph16040483 - 23 Mar 2023
Viewed by 1146
Abstract
Chondroitin sulfate (CS), a well-known glycosaminoglycan, was physically crosslinked with Fe(III), Gd(III), Zn(II), and Cu(II) ions to obtain CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) polymeric particles for multipurpose biological applications. The CS–metal ion-containing particles in the micrometer to a few hundred nanometer size range [...] Read more.
Chondroitin sulfate (CS), a well-known glycosaminoglycan, was physically crosslinked with Fe(III), Gd(III), Zn(II), and Cu(II) ions to obtain CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) polymeric particles for multipurpose biological applications. The CS–metal ion-containing particles in the micrometer to a few hundred nanometer size range are injectable materials for intravenous administration. The CS–metal ion-containing particles are safe biomaterials for biological applications because of their perfect blood compatibility and no significant cytotoxicity on L929 fibroblast cells up to a 10 mg/mL concentration. Furthermore, CS-Zn(II) and CS-Cu(II) particles show excellent antibacterial susceptibility, with 2.5–5.0 mg/mL minimum inhibition concentration (MIC) values against Escherichia coli and Staphylococcus aureus. Moreover, the in vitro contrast enhancement abilities of aqueous CS–metal ion particle suspensions in magnetic resonance imaging (MRI) were determined by obtaining T1- and T2-weighted MR images using a 0.5 Tesla MRI scanner and by calculating the water proton relaxivities. Therefore, these CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) particles have significant potential as antibacterial additive materials and MRI contrast enhancement agents with less toxicity. Full article
(This article belongs to the Special Issue Molecular Systems for the Delivery of Drugs and Contrast Agents)
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14 pages, 1880 KiB  
Article
Peptide-Based Hydrogels and Nanogels Containing Gd(III) Complexes as T1 Relaxation Agents
by
Elisabetta Rosa
,
Fabio Carniato
,
Lorenzo Tei
,
Carlo Diaferia
,
Giancarlo Morelli
,
Mauro Botta
and
Antonella Accardo
Pharmaceuticals 2022, 15(12), 1572; https://doi.org/10.3390/ph15121572 - 16 Dec 2022
Cited by 4 | Viewed by 1064
Abstract
New peptide-based hydrogels incorporating Gd(III) chelates with different hydration states, molecular structures and overall negative charges ([Gd(BOPTA)]2−), [Gd(DTPA)]2−, and ([Gd(AAZTA)]−) were prepared and characterized. N-terminal Fmoc- or acetyl-derivatized hexapeptides (K1, K2 and K3) containing five aliphatic amino [...] Read more.
New peptide-based hydrogels incorporating Gd(III) chelates with different hydration states, molecular structures and overall negative charges ([Gd(BOPTA)]2−), [Gd(DTPA)]2−, and ([Gd(AAZTA)]−) were prepared and characterized. N-terminal Fmoc- or acetyl-derivatized hexapeptides (K1, K2 and K3) containing five aliphatic amino acids (differently ordered Gly, Ala, Val, Leu and Ile) and a charged lysine at the amidated C-terminal were used for the formation of the hydrogels. Particular attention was paid to the investigation of the morphological and rheological properties of the nanoparticles, in addition to the assessment of the ability (relaxivity) of the confined complexes to accelerate the longitudinal relaxation rate of the water protons localized in the polymeric network. The relaxivity values at high magnetic fields (>0.5 T) of the paramagnetic hydrogels appear to be more than five times higher than those of isolated chelates in an aqueous solution, reaching a value of 25 mmol−1 s−1 for Fmoc-K2+[Gd(BOPTA)]2− at 0.5 T and 310 K. Furthermore, an interesting trend of decrease of relaxivity with increasing the degree of rigidity of the hydrogel was observed. The type of interactions between the various complexes and the polymeric network also plays a key role in influencing the relaxivity values of the final materials. Nanogels were also obtained from the submicronization of the hydrogel containing [Gd(BOPTA)]2− chelate. Circular dichroism, dynamic light scattering and relaxometric investigations on these nanoparticles revealed the formation of nanogels endowed with higher relaxivities (r1 = 41 mM−1 s−1 at 0.5 T MHz and 310 K) than the corresponding hydrogels. Full article
(This article belongs to the Special Issue Molecular Systems for the Delivery of Drugs and Contrast Agents)
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14 pages, 3732 KiB  
Article
Oxidative Stress-Induced Silver Nano-Carriers for Chemotherapy
by
Minh Phuong Nguyen
,
Duy Phong Pham
and
Dukjoon Kim
Pharmaceuticals 2022, 15(12), 1449; https://doi.org/10.3390/ph15121449 - 22 Nov 2022
Cited by 1 | Viewed by 863
Abstract
Recently, silver nanoparticles (AgNPs) have been extensively explored in a variety of biological applications, especially cancer treatment. AgNPs have been demonstrated to exhibit anti-tumor effects through cell apoptosis. This study intends to promote cell apoptosis further by increasing oxidative stress. AgNPs are encapsulated [...] Read more.
Recently, silver nanoparticles (AgNPs) have been extensively explored in a variety of biological applications, especially cancer treatment. AgNPs have been demonstrated to exhibit anti-tumor effects through cell apoptosis. This study intends to promote cell apoptosis further by increasing oxidative stress. AgNPs are encapsulated by biocompatible and biodegradable polyaspartamide (PA) (PA-AgNPs) that carries the anti-cancer drug Doxorubicin (Dox) to inhibit cancer cells primarily. PA-AgNPs have an average hydrodynamic diameter of 130 nm, allowing them to move flexibly within the body. PA-AgNPs show an excellent targeting capacity to cancer cells when they are conjugated to biotin. In addition, they release Dox efficiently by up to 88% in cancer environments. The DCFDA experiment demonstrates that the Dox-carried PA-AgNPs generate reactive oxidation species intensively beside 4T1 cells. The MTT experiment confirms that PA-AgNPs with Dox may strongly inhibit 4T1 cancer cells. Furthermore, the in vivo study confirms that PA-AgNPs with Dox successfully inhibit tumors, which are about four times smaller than the control group and have high biosafety that can be applied for chemotherapy. Full article
(This article belongs to the Special Issue Molecular Systems for the Delivery of Drugs and Contrast Agents)
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Review

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35 pages, 11945 KiB  
Review
Exploration of NIR Squaraine Contrast Agents Containing Various Heterocycles: Synthesis, Optical Properties and Applications
by
Shahir Sarasiya
,
Sara Sarasiya
and
Maged Henary
Pharmaceuticals 2023, 16(9), 1299; https://doi.org/10.3390/ph16091299 - 14 Sep 2023
Viewed by 553
Abstract
Squaraine dye is a popular class of contrast near-infrared (NIR) dyes. Squaraine dyes have shown the ability to be modified with various heterocycles. The indole moiety is the most notable heterocycle incorporated in squaraine dyes. A tremendous amount of work has gone into [...] Read more.
Squaraine dye is a popular class of contrast near-infrared (NIR) dyes. Squaraine dyes have shown the ability to be modified with various heterocycles. The indole moiety is the most notable heterocycle incorporated in squaraine dyes. A tremendous amount of work has gone into developing indole-based squaraine dyes and determining their applications. The optical properties of squaraine dyes containing an indole moiety facilitate high quantum yields and molar absorptivity, but the absorbance maxima is capped near 700 nm. This is the major limitation of indole-based squaraine dyes. In comparison, other heterocycles with larger conjugated systems such as quinoline and perimidine have demonstrated promising optical properties and immense potential for modifications, albeit with limited development. Quinoline- and perimidine-based squaraine dyes have molar extinction coefficients over 100,000 M−1 cm−1 and absorbances over 800 nm. This report will look at indole-, quinoline-, and perimidine-based squaraine dyes. Due to the sheer number of reported dyes, the search for indole-based squaraine dyes has been limited to reports from the past five years (2018–2023). For quinoline- and perimidine-based squaraine dyes, a holistic search was performed to analyze the optical properties and applications, due to the abovementioned limitation. This report will evaluate the three different classes of squaraines: indole-, quinoline-, and perimidine-based, to evaluate their optical properties and applications, with the goal of encouraging the exploration of other heterocycles for use in squaraine dyes. Full article
(This article belongs to the Special Issue Molecular Systems for the Delivery of Drugs and Contrast Agents)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Tentative Title: Multitarget systems for drug delivery and detection: up-to-date strategies for brain disorders

Clara Grosso*, Cristina Delerue-Matos, M. Fátima Barroso

 

Requimte/LAQV, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto,

Rua Dr. António Bernardino de Almeida 431, 4249-015 Porto, Portugal

 

Tentative Abstract: Currently, multi-targeted therapy seems to be the most promising strategy in the fight against diseases of a multifactorial nature, such as neuropsychiatric and neurodegenerative diseases. The use of this strategy allows acting on multiple targets involved in the pathogenesis and progression of these disorders, offering advantages over the single target therapy.

Therefore, this review summarizes the recent findings on the development of different types of multitarget nanoparticles for detection and drug delivery to brain, focusing on promising active principles encapsulated, nanoparticles surface modification and functionalization able to detect or target different brain regions and cells.

 

Keywords: nanoparticles; drug delivery; multifactorial disorders

 

 

Tentative Title:  Physically crosslinked chondroitin sulfate (CS)-Metal ions (M:Fe(III), Gd(III), Zn(II), and Cu(II)) particles for versatile applications and their biosafety
 
Selin S. Suner, Mehtap Sahiner, Evrim Umut, Ramesh S. Ayyala, * Nurettin Sahiner
 
Department of Chemistry, and Nanoscience and Technology Research and Application Center, Canakkale Onsekiz Mart University, Terzioglu Campus, 17100, Canakkale, Turkey.
 
Department of Bioengineering, Canakkale Onsekiz Mart University, 17100, Canakkale, Turkey
 
Department of Medical Imaging Techniques, School of Healthcare, Dokuz Eylul University, Narlıdere - Izmir, 35330, Turkey.
 
Department of Chemical and Biomolecular Engineering, University of South Florida, Tampa, FL, 33620, USA.
 
Department of Ophthalmology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs B. Downs Blv., MDC 21, Tampa, FL 33612, USA.
 
Tentative Abstract
Chondroitin sulfate (CS), a well-known glycosaminoglycan, was physically crosslinked with Fe(III), Gd(III), Zn(II), and Cu(II) ions to obtain CS-Fe(III), CS-Gd(III), CS-Zn(II) and CS-Cu(II) polymeric particles for multipurpose biological applications. The CS-Metal ion containing particles in the micrometer to a few hundreds of nanometer size range are injectable materials for intravenous administration. The CS-Metal ion particles were tested for blood compatibility via hemolysis and blood clotting assays.
The cytotoxicity of CS-Metal ion particles was also determined on healthy L929 fibroblast cells. The minimum inhibition concentration (MIC) values and inhibition zone of CS-Metal ion particles were determined against various gram-positive and gram-negative bacteria strains by using microtiter and disc diffusion assays to assess the antibacterial susceptibility of the particles. Moreover,/ in vitro/ contrast-enhancing abilities of CS-Metal ion particles in magnetic resonance imaging (MRI) were determined by photon density images using an MRI scanner and their photon relativities.
 
*Keywords: *Chondroitin sulfate (CS), CS-Metal ion particles, biocompatible, antibacterial, Magnetic resonance imaging (MRI).

 

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