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Pharmaceutics
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Supramolecular Systems for Gene and Drug Delivery, 2nd Edition
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Supramolecular Systems for Gene and Drug Delivery, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 10 June 2024 | Viewed by 14058

Special Issue Editors

Dr. Francisco José Ostos

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Guest Editor
Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, 41013 Seville, Spain
Interests: DNA; calixarenes; liposomes; drugs; micelles; vesicles; nanovehicles; nanoparticles
Special Issues, Collections and Topics in MDPI journals
Dr. José Antonio Lebrón

E-Mail Website
Guest Editor
Department of Physical Chemistry, University of Seville, c/Profesor García González, 1 41012 Seville, Spain
Interests: surfactants; nanoparticles; micelles; liposome; drug delivery
Prof. Dr. Pilar López-Cornejo

E-Mail Website
Guest Editor
Department of Physical Chemistry, Faculty of Chemistry, University of Seville, Prof. García González nº 1, 41012 Seville, Spain
Interests: nanomaterials; polymers; physical chemistry; Kinetics; thermodynamics; carbon nanotubes; DNA; gene therapy; micelles; liposomes; nanoparticles; dendrimers; surfactants
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Supramolecular systems (calixarenes, cyclodextrins, polymers, peptides, etc.) have attracted special attention due to their excellent therapeutic properties for biomedical applications, such as gene and drug delivery. Numerous biomaterials-based supramolecular systems have been developed in the last decade for enhancing of biocompatibility and pharmacological activity. In particular, supramolecular nanomaterials are considered a hot research topic, because nanomedicine has become an interesting tool for the treatment of genetic diseases or cancer. Nevertheless, novel systems and their properties are being continuously studied, contributing to the development of efficient delivery systems.

This Special Issue provides and highlights current progress in the use of the supramolecular systems for boosting gene and drug delivery. Preparation, characterization, and use of these systems, as well as the latest developments in this research field, are especially welcome.

Authors are encouraged to submit original research articles and reviews in this promising research field.

Dr. Francisco José Ostos
Dr. José Antonio Lebrón
Prof. Dr. Pilar López-Cornejo
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. Pharmaceutics 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

  • supramolecular materials
  • gene and drug delivery systems
  • nanomaterials
  • controlled release
  • drug targeting
  • polymers
  • peptides
  • macrocycles

Published Papers (7 papers)

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Research

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21 pages, 4321 KiB  
Article
Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects
by José David Celdrán, Lawrence Humphreys, Desirée González, Cristina Soto-Sánchez, Gema Martínez-Navarrete, Iván Maldonado, Idoia Gallego, Ilia Villate-Beitia, Myriam Sainz-Ramos, Gustavo Puras, José Luis Pedraz and Eduardo Fernández
Pharmaceutics 2023, 15(7), 1860; https://doi.org/10.3390/pharmaceutics15071860 - 01 Jul 2023
Viewed by 1271
Abstract
Gene therapy and optogenetics are becoming promising tools for treating several nervous system pathologies. Currently, most of these approaches use viral vectors to transport the genetic material inside the cells, but viruses present some potential risks, such as marked immunogenicity, insertional mutagenesis, and [...] Read more.
Gene therapy and optogenetics are becoming promising tools for treating several nervous system pathologies. Currently, most of these approaches use viral vectors to transport the genetic material inside the cells, but viruses present some potential risks, such as marked immunogenicity, insertional mutagenesis, and limited insert gene size. In this framework, non-viral nanoparticles, such as niosomes, are emerging as possible alternative tools to deliver genetic material, avoiding the aforementioned problems. To determine their suitability as vectors for optogenetic therapies in this work, we tested three different niosome formulations combined with three optogenetic plasmids in rat cortical neurons in vitro. All niosomes tested successfully expressed optogenetic channels, which were dependent on the ratio of niosome to plasmid, with higher concentrations yielding higher expression rates. However, we found changes in the dendritic morphology and electrophysiological properties of transfected cells, especially when we used higher concentrations of niosomes. Our results highlight the potential use of niosomes for optogenetic applications and suggest that special care must be taken to achieve an optimal balance of niosomes and nucleic acids to achieve the therapeutic effects envisioned by these technologies. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
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16 pages, 4570 KiB  
Article
Cataleptogenic Effect of Haloperidol Formulated in Water-Soluble Calixarene-Based Nanoparticles
by Nadezda E. Kashapova, Ruslan R. Kashapov, Albina Y. Ziganshina, Dmitry O. Nikitin, Irina I. Semina, Vadim V. Salnikov, Vitaliy V. Khutoryanskiy, Rouslan I. Moustafine and Lucia Y. Zakharova
Pharmaceutics 2023, 15(3), 921; https://doi.org/10.3390/pharmaceutics15030921 - 11 Mar 2023
Cited by 3 | Viewed by 1588
Abstract
In this study, a water-soluble form of haloperidol was obtained by coaggregation with calix[4]resorcinol bearing viologen groups on the upper rim and decyl chains on the lower rim to form vesicular nanoparticles. The formation of nanoparticles is achieved by the spontaneous loading of [...] Read more.
In this study, a water-soluble form of haloperidol was obtained by coaggregation with calix[4]resorcinol bearing viologen groups on the upper rim and decyl chains on the lower rim to form vesicular nanoparticles. The formation of nanoparticles is achieved by the spontaneous loading of haloperidol into the hydrophobic domains of aggregates based on this macrocycle. The mucoadhesive and thermosensitive properties of calix[4]resorcinol–haloperidol nanoparticles were established by UV-, fluorescence and CD spectroscopy data. Pharmacological studies have revealed low in vivo toxicity of pure calix[4]resorcinol (LD50 is 540 ± 75 mg/kg for mice and 510 ± 63 mg/kg for rats) and the absence of its effect on the motor activity and psycho-emotional state of mice, which opens up a possibility for its use in the design of effective drug delivery systems. Haloperidol formulated with calix[4]resorcinol exhibits a cataleptogenic effect in rats both when administered intranasally and intraperitoneally. The effect of the intranasal administration of haloperidol with macrocycle in the first 120 min is comparable to the effect of commercial haloperidol, but the duration of catalepsy was shorter by 2.9 and 2.3 times (p < 0.05) at 180 and 240 min, respectively, than that of the control. There was a statistically significant reduction in the cataleptogenic activity at 10 and 30 min after the intraperitoneal injection of haloperidol with calix[4]resorcinol, then there was an increase in the activity by 1.8 times (p < 0.05) at 60 min, and after 120, 180 and 240 min the effect of this haloperidol formulation was at the level of the control sample. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
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14 pages, 2675 KiB  
Article
Single -and Multi-Walled Carbon Nanotubes as Nanocarriers for the Delivery of 7-Hydroxyflavone
by Cecilia Espíndola, Alejandro Javier Correa, Manuel López-López, Pilar López-Cornejo, Eva Bernal, José Antonio Lebrón, Francisco José Ostos, Mohammed Rafii-El-Idrissi Benhnia and María Luisa Moyá
Pharmaceutics 2022, 14(12), 2806; https://doi.org/10.3390/pharmaceutics14122806 - 15 Dec 2022
Cited by 4 | Viewed by 1440
Abstract
The research on flavonoids has exponentially grown since their first therapeutic evidence, in 1937. They are effective in vitro in a wide range of human diseases, particularly those mediated by free radicals, such as cancer, atherosclerosis, AIDS, or neuronal diseases. However, their applications [...] Read more.
The research on flavonoids has exponentially grown since their first therapeutic evidence, in 1937. They are effective in vitro in a wide range of human diseases, particularly those mediated by free radicals, such as cancer, atherosclerosis, AIDS, or neuronal diseases. However, their applications have been reduced due to their low solubility, poor absorption, and rapid metabolism. Flavonoid encapsulation in nanocarriers significantly improves their oral absorption, protects the drug against degradation, decreases the first-pass hepatic effect, and makes absorption through the lymphatic system easier. In this work, carbon nanotubes were used as nanocarriers of 7-hydroxyflavone, 7-HF. The encapsulation of 7-HF into pristine single- and multi-walled carbon nanotubes, and into -COOH functionalized single-walled carbon nanotubes has been investigated. The equilibrium association constants were estimated. The structural backbone of 7-HF, two benzene rings linked through three carbon atoms that form a pyran heterocyclic ring containing a keto group, seems to play a key role in the 7-HF/CNT interactions, although other types of interactions are also at work. The in vitro release of 7-HF was studied at three pHs, 2.0, 7.4, and 9.2, mimicking the different biological barriers of the human organism. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
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13 pages, 3355 KiB  
Article
L-Serine-Modified Poly-L-Lysine as a Biodegradable Kidney-Targeted Drug Carrier for the Efficient Radionuclide Therapy of Renal Cell Carcinoma
by Hidemasa Katsumi, Sho Kitada, Shintaro Yasuoka, Rie Takashima, Tomoki Imanishi, Rina Tanaka, Satoru Matsuura, Hiroyuki Kimura, Hidekazu Kawashima, Masaki Morishita and Akira Yamamoto
Pharmaceutics 2022, 14(9), 1946; https://doi.org/10.3390/pharmaceutics14091946 - 14 Sep 2022
Cited by 1 | Viewed by 1306
Abstract
In the present study, L-serine (Ser)-modified poly-L-lysine (PLL) was synthesized to develop a biodegradable, kidney-targeted drug carrier for efficient radionuclide therapy in renal cell carcinoma (RCC). Ser-PLL was labeled with 111In/90Y via diethylenetriaminepentaacetic acid (DTPA) chelation for biodistribution analysis/radionuclide therapy. [...] Read more.
In the present study, L-serine (Ser)-modified poly-L-lysine (PLL) was synthesized to develop a biodegradable, kidney-targeted drug carrier for efficient radionuclide therapy in renal cell carcinoma (RCC). Ser-PLL was labeled with 111In/90Y via diethylenetriaminepentaacetic acid (DTPA) chelation for biodistribution analysis/radionuclide therapy. In mice, approximately 91% of the total dose accumulated in the kidney 3 h after intravenous injection of 111In-labeled Ser-PLL. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging showed that 111In-labeled Ser-PLL accumulated in the renal cortex following intravenous injection. An intrarenal distribution study showed that fluorescein isothiocyanate (FITC)-labeled Ser-PLL accumulated mainly in the renal proximal tubules. This pattern was associated with RCC pathogenesis. Moreover, 111In-labeled Ser-PLL rapidly degraded and was eluted along with the low-molecular-weight fractions of the renal homogenate in gel filtration chromatography. Continuous Ser-PLL administration over five days had no significant effect on plasma creatinine, blood urea nitrogen (BUN), or renal histology. In a murine RCC model, kidney tumor growth was significantly inhibited by the administration of the beta-emitter 90Y combined with Ser-PLL. The foregoing results indicate that Ser-PLL is promising as a biodegradable drug carrier for kidney-targeted drug delivery and efficient radionuclide therapy in RCC. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
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14 pages, 4539 KiB  
Article
Antifungal Potential of Synthetic Peptides against Cryptococcus neoformans: Mechanism of Action Studies Reveal Synthetic Peptides Induce Membrane–Pore Formation, DNA Degradation, and Apoptosis
by Tawanny K. B. Aguiar, Nilton A. S. Neto, Cleverson D. T. Freitas, Ayrles F. B. Silva, Leandro P. Bezerra, Ellen A. Malveira, Levi A. C. Branco, Felipe P. Mesquita, Gustavo H. Goldman, Luciana M. R. Alencar, Jose T. A. Oliveira, Ralph Santos-Oliveira and Pedro F. N. Souza
Pharmaceutics 2022, 14(8), 1678; https://doi.org/10.3390/pharmaceutics14081678 - 12 Aug 2022
Cited by 7 | Viewed by 2099
Abstract
Cryptococcus neoformans is a human-pathogenic yeast responsible for pneumonia and meningitis, mainly in patients immunocompromised. Infections caused by C. neoformans are a global health concern. Synthetic antimicrobial peptides (SAMPs) have emerged as alternative molecules to cope with fungal infections, including C. neoformans. [...] Read more.
Cryptococcus neoformans is a human-pathogenic yeast responsible for pneumonia and meningitis, mainly in patients immunocompromised. Infections caused by C. neoformans are a global health concern. Synthetic antimicrobial peptides (SAMPs) have emerged as alternative molecules to cope with fungal infections, including C. neoformans. Here, eight SAMPs were tested regarding their antifungal potential against C. neoformans and had their mechanisms of action elucidated by fluorescence and scanning electron microscopies. Five SAMPs showed an inhibitory effect (MIC50) on C. neoformans growth at low concentrations. Fluorescence microscope (FM) revealed that SAMPs induced 6-kDa pores in the C. neoformans membrane. Inhibitory assays in the presence of ergosterol revealed that some peptides lost their activity, suggesting interaction with it. Furthermore, FM analysis revealed that SAMPs induced caspase 3/7-mediated apoptosis and DNA degradation in C. neoformans cells. Scanning Electron Microscopy (SEM) analysis revealed that peptides induced many morphological alterations such as cell membrane, wall damage, and loss of internal content on C. neoformans cells. Our results strongly suggest synthetic peptides are potential alternative molecules to control C. neoformans growth and treat the cryptococcal infection. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
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Review

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18 pages, 1111 KiB  
Review
The Human Dermis as a Target of Nanoparticles for Treating Skin Conditions
by Javier Salazar, Thais Carmona, Flavia C. Zacconi, Diego Venegas-Yazigi, Claudio Cabello-Verrugio, Won Il Choi and Cristian Vilos
Pharmaceutics 2023, 15(1), 10; https://doi.org/10.3390/pharmaceutics15010010 - 20 Dec 2022
Cited by 6 | Viewed by 2900
Abstract
Skin has a preventive role against any damage raised by harmful microorganisms and physical and chemical assaults from the external environment that could affect the body’s internal organs. Dermis represents the main section of the skin, and its contribution to skin physiology is [...] Read more.
Skin has a preventive role against any damage raised by harmful microorganisms and physical and chemical assaults from the external environment that could affect the body’s internal organs. Dermis represents the main section of the skin, and its contribution to skin physiology is critical due to its diverse cellularity, vasculature, and release of molecular mediators involved in the extracellular matrix maintenance and modulation of the immune response. Skin structure and complexity limit the transport of substances, promoting the study of different types of nanoparticles that penetrate the skin layers under different mechanisms intended for skin illness treatments and dermo-cosmetic applications. In this work, we present a detailed morphological description of the dermis in terms of its structures and resident cells. Furthermore, we analyze the role of the dermis in regulating skin homeostasis and its alterations in pathophysiological conditions, highlighting its potential as a therapeutic target. Additionally, we describe the use of nanoparticles for skin illness treatments focused on dermis release and promote the use of metal-organic frameworks (MOFs) as an integrative strategy for skin treatments. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
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38 pages, 5257 KiB  
Review
An Overview of the Supramolecular Systems for Gene and Drug Delivery in Tissue Regeneration
by Saketh Reddy Ranamalla, Alina Silvia Porfire, Ioan Tomuță and Manuela Banciu
Pharmaceutics 2022, 14(8), 1733; https://doi.org/10.3390/pharmaceutics14081733 - 18 Aug 2022
Cited by 2 | Viewed by 2252
Abstract
Tissue regeneration is a prominent area of research, developing biomaterials aimed to be tunable, mechanistic scaffolds that mimic the physiological environment of the tissue. These biomaterials are projected to effectively possess similar chemical and biological properties, while at the same time are required [...] Read more.
Tissue regeneration is a prominent area of research, developing biomaterials aimed to be tunable, mechanistic scaffolds that mimic the physiological environment of the tissue. These biomaterials are projected to effectively possess similar chemical and biological properties, while at the same time are required to be safely and quickly degradable in the body once the desired restoration is achieved. Supramolecular systems composed of reversible, non-covalently connected, self-assembly units that respond to biological stimuli and signal cells have efficiently been developed as preferred biomaterials. Their biocompatibility and the ability to engineer the functionality have led to promising results in regenerative therapy. This review was intended to illuminate those who wish to envisage the niche translational research in regenerative therapy by summarizing the various explored types, chemistry, mechanisms, stimuli receptivity, and other advancements of supramolecular systems. Full article
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery, 2nd Edition)
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