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Pharmaceutics
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Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications
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Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 12125

Special Issue Editors

Dr. Ionela Cristina Nica

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Guest Editor
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
Interests: nanomedicine; biomaterials; toxicology; biological response; tissue engineering; materials characterization
Special Issues, Collections and Topics in MDPI journals
Dr. Sorina Nicoleta Petrache Voicu

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
Interests: nanotoxicology; nanomedicine; proteomics; ceall death; oxidative stress; nanoparticles; gadolinium nanogels; quantum dots; human and murine melanoma animal models

Special Issue Information

Dear Colleagues,

Nanotechnology is a promising tool with a wide range of advantages and applications in the medical field. For decades pharmaceutical sciences have been using nanoparticles to reduce toxicity and side effects of drugs. In clinical practice, many nanodrugs have been used for both diagnostic and therapeutic applications. Nanoparticles are used for the cure of kidney diseases, tuberculosis, skin conditions, Alzheimer’s disease, different types of cancer as well as preparation of COVID-19 vaccines. Since there is a vast area of possibilities for the chemical composition of engineered nanomaterials, this Special Issue will focus on recent advances in nanomedical applications and on new synthesis routes of different types of nanosystems (carbon nanotubes, paramagnetic nanoparticles, dendrimers, nanoemulsions, etc.) designed for pharmaceutics. In this regard, we cordially invite the researchers working in the field to submit their contributions on these aspects or other topics relevant to the theme. Original research articles, reviews and communications are all welcome.

Dr. Ionela Cristina Nica
Dr. Sorina Nicoleta Petrache Voicu
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

  • nanoparticles
  • drug delivery
  • biological barriers
  • pharmaceutical
  • diagnosis
  • therapy
  • efficacy and safety assessment
  • in vitro and in vivo studies

Published Papers (7 papers)

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Research

Jump to: Review

23 pages, 3962 KiB  
Article
Biomedical Promise of Sustainable Microwave-Engineered Symmetric Curcumin Derivatives
by Cristina Doina Niţu, Maria Mernea, Raluca Ioana Vlasceanu, Bianca Voicu-Balasea, Madalina Andreea Badea, Florentina Monica Raduly, Valentin Rădiţoiu, Alina Rădiţoiu, Speranta Avram, Dan F. Mihailescu, Ionela C. Voinea and Miruna Silvia Stan
Pharmaceutics 2024, 16(2), 205; https://doi.org/10.3390/pharmaceutics16020205 - 31 Jan 2024
Viewed by 732
Abstract
Curcumin is a polyphenol of the Curcuma longa plant, which can be used for various medicinal purposes, such as inflammation and cancer treatment. In this context, two symmetric curcumin derivatives (D1—(1E,6E)-1,7-bis(4-acetamidophenyl)hepta-1,6-diene-3,5-dione and D2—p,p-dihydroxy di-cinnamoyl methane) were obtained by the microwave-based method and evaluated [...] Read more.
Curcumin is a polyphenol of the Curcuma longa plant, which can be used for various medicinal purposes, such as inflammation and cancer treatment. In this context, two symmetric curcumin derivatives (D1—(1E,6E)-1,7-bis(4-acetamidophenyl)hepta-1,6-diene-3,5-dione and D2—p,p-dihydroxy di-cinnamoyl methane) were obtained by the microwave-based method and evaluated for their antitumoral effect on human cervix cancer in comparison with toxicity on non-tumoral cells, taking into account that they were predicted to act as apoptosis agonists or anti-inflammatory agents. The HeLa cell line was incubated for 24 and 72 h with a concentration of 50 μg/mL of derivatives that killed almost half of the cells compared to the control. In contrast, these compounds did not alter the viability of MRC-5 non-tumoral lung fibroblasts until 72 h of incubation. The nitric oxide level released by HeLa cells was higher compared to MRC-5 fibroblasts after the incubation with 100 μg/mL. Both derivatives induced the decrease of catalase activity and glutathione levels in cancer cells without targeting the same effect in non-tumoral cells. Furthermore, the Western blot showed an increased protein expression of HSP70 and a decreased expression of HSP60 and MCM2 in cells incubated with D2 compared to control cells. We noticed differences regarding the intensity of cell death between the tested derivatives, suggesting that the modified structure after synthesis can modulate their function, the most prominent effect being observed for sample D2. In conclusion, the outcomes of our in vitro study revealed that these microwave-engineered curcumin derivatives targeted tumor cells, much more specifically, inducing their death. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications)
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17 pages, 2870 KiB  
Article
Utilizing Molecular Simulations to Examine Nanosuspension Stability
by Andrew P. Latham, Elizabeth S. Levy, Benjamin D. Sellers and Dennis H. Leung
Pharmaceutics 2024, 16(1), 50; https://doi.org/10.3390/pharmaceutics16010050 - 28 Dec 2023
Viewed by 804
Abstract
Drug nanosuspensions offer a promising approach to improve bioavailability for poorly soluble drug candidates. Such formulations often necessitate the inclusion of an excipient to stabilize the drug nanoparticles. However, the rationale for the choice of the correct excipient for a given drug candidate [...] Read more.
Drug nanosuspensions offer a promising approach to improve bioavailability for poorly soluble drug candidates. Such formulations often necessitate the inclusion of an excipient to stabilize the drug nanoparticles. However, the rationale for the choice of the correct excipient for a given drug candidate remains unclear. To gain molecular insight into formulation design, this work first utilizes a molecular dynamics simulation to computationally investigate drug–excipient interactions for a number of combinations that have been previously studied experimentally. We find that hydrophobic interactions drive excipient adsorption to drug nanoparticles and that the fraction of polar surface area serves as a predictor for experimental measurements of nanosuspension stability. To test these ideas prospectively, we applied our model to an uncharacterized drug compound, GDC-0810. Our simulations predicted that a salt form of GDC-0810 would lead to more stable nanosuspensions than the neutral form; therefore, we tested the stability of salt GDC-0810 nanosuspensions and found that the salt form readily formed nanosuspensions even without the excipient. To avoid computationally expensive simulations in the future, we extended our model by showing that simple, two-dimensional properties of single drug molecules can be used to rationalize nanosuspension designs without simulations. In all, our work demonstrates how computational tools can provide molecular insight into drug–excipient interactions and aid in rational formulation design. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications)
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10 pages, 4537 KiB  
Communication
Activation of Insulin Gene Expression via Transfection of a CRISPR/dCas9a System Using Magnetic Peptide-Imprinted Nanoparticles
by Mei-Hwa Lee, James L. Thomas, Chien-Yu Lin, Yi-Chen Ethan Li and Hung-Yin Lin
Pharmaceutics 2023, 15(4), 1311; https://doi.org/10.3390/pharmaceutics15041311 - 21 Apr 2023
Cited by 1 | Viewed by 1346
Abstract
A CRISPRa transcription activation system was used to upregulate insulin expression in HEK293T cells. To increase the delivery of the targeted CRISPR/dCas9a, magnetic chitosan nanoparticles, imprinted with a peptide from the Cas9 protein, were developed, characterized, and then bound to dCas9a that was [...] Read more.
A CRISPRa transcription activation system was used to upregulate insulin expression in HEK293T cells. To increase the delivery of the targeted CRISPR/dCas9a, magnetic chitosan nanoparticles, imprinted with a peptide from the Cas9 protein, were developed, characterized, and then bound to dCas9a that was complexed with a guide RNA (gRNA). The adsorption of dCas9 proteins conjugated with activators (SunTag, VPR, and p300) to the nanoparticles was monitored using both ELISA kits and Cas9 staining. Finally, the nanoparticles were used to deliver dCas9a that was complexed with a synthetic gRNA into HEK293T cells to activate their insulin gene expression. Delivery and gene expression were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and staining of insulin. Finally, the long-term release of insulin and the cellular pathway related to stimulation by glucose were also investigated. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications)
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22 pages, 12996 KiB  
Article
Photodynamic Activity of TMPyP4/TiO2 Complex under Blue Light in Human Melanoma Cells: Potential for Cancer-Selective Therapy
by Mihaela Balas, Simona Nistorescu, Madalina Andreea Badea, Anca Dinischiotu, Mihai Boni, Andra Dinache, Adriana Smarandache, Ana-Maria Udrea, Petronela Prepelita and Angela Staicu
Pharmaceutics 2023, 15(4), 1194; https://doi.org/10.3390/pharmaceutics15041194 - 09 Apr 2023
Cited by 3 | Viewed by 1913
Abstract
The combination of TiO2 nanoparticles (NPs) and photosensitizers (PS) may offer significant advantages in photodynamic therapy (PDT) of melanoma, such as improved cell penetration, enhanced ROS production, and cancer selectivity. In this study, we aimed to investigate the photodynamic effect of 5,10,15,20-(Tetra-N-methyl-4-pyridyl)porphyrin [...] Read more.
The combination of TiO2 nanoparticles (NPs) and photosensitizers (PS) may offer significant advantages in photodynamic therapy (PDT) of melanoma, such as improved cell penetration, enhanced ROS production, and cancer selectivity. In this study, we aimed to investigate the photodynamic effect of 5,10,15,20-(Tetra-N-methyl-4-pyridyl)porphyrin tetratosylate (TMPyP4) complexes with TiO2 NPs on human cutaneous melanoma cells by irradiation with 1 mW/cm2 blue light. The porphyrin conjugation with the NPs was analyzed by absorption and FTIR spectroscopy. The morphological characterization of the complexes was performed by Scanning Electron Microscopy and Dynamic Light Scattering. The singlet oxygen generation was analyzed by phosphorescence at 1270 nm. Our predictions indicated that the non-irradiated investigated porphyrin has a low degree of toxicity. The photodynamic activity of the TMPyP4/TiO2 complex was assessed on the human melanoma Mel-Juso cell line and non-tumor skin CCD-1070Sk cell line treated with various concentrations of the PS and subjected to dark conditions and visible light-irradiation. The tested complexes of TiO2 NPs with TMPyP4 presented cytotoxicity only after activation by blue light (405 nm) mediated by the intracellular production of ROS in a dose-dependent manner. The photodynamic effect observed in this evaluation was higher in melanoma cells than the effect observed in the non-tumor cell line, demonstrating a promising potential for cancer-selectivity in PDT of melanoma. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications)
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16 pages, 2898 KiB  
Article
Optimizing Dacarbazine Therapy: Design of a Laser-Triggered Delivery System Based on β-Cyclodextrin and Plasmonic Gold Nanoparticles
by Sebastián Quintana-Contardo, Orlando Donoso-González, Erika Lang, Ariel R. Guerrero, Michael Noyong, Ulrich Simon, Marcelo J. Kogan, Nicolás Yutronic and Rodrigo Sierpe
Pharmaceutics 2023, 15(2), 458; https://doi.org/10.3390/pharmaceutics15020458 - 30 Jan 2023
Cited by 3 | Viewed by 2022
Abstract
Dacarbazine (DB) is an antineoplastic drug extensively used in cancer therapy. However, present limitations on its performance are related to its low solubility, instability, and non-specificity. To overcome these drawbacks, DB was included in β-cyclodextrin (βCD), which increased its aqueous solubility and stability. [...] Read more.
Dacarbazine (DB) is an antineoplastic drug extensively used in cancer therapy. However, present limitations on its performance are related to its low solubility, instability, and non-specificity. To overcome these drawbacks, DB was included in β-cyclodextrin (βCD), which increased its aqueous solubility and stability. This new βCD@DB complex has been associated with plasmonic gold nanoparticles (AuNPs), and polyethylene glycol (PEG) has been added in the process to increase the colloidal stability and biocompatibility. Different techniques revealed that DB allows for a dynamic inclusion into βCD, with an association constant of 80 M−1 and a degree of solubilization of 0.023, where βCD showed a loading capacity of 16%. The partial exposure of the NH2 group in the included DB allows its interaction with AuNPs, with a loading efficiency of 99%. The PEG-AuNPs-βCD@DB nanosystem exhibits an optical plasmonic absorption at 525 nm, a surface charge of −29 mV, and an average size of 12 nm. Finally, laser irradiation assays showed that DB can be released from this platform in a controlled manner over time, reaching a concentration of 56 μg/mL (43% of the initially loaded amount), which, added to the previous data, validates its potential for drug delivery applications. Therefore, the novel nanosystem based on βCD, AuNPs, and PEG is a promising candidate as a new nanocarrier for DB. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications)
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15 pages, 2230 KiB  
Article
Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System
by Marzia Cirri, Giulia Nerli, Natascia Mennini, Francesca Maestrelli and Paola Mura
Pharmaceutics 2022, 14(12), 2567; https://doi.org/10.3390/pharmaceutics14122567 - 23 Nov 2022
Cited by 3 | Viewed by 1754
Abstract
Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective drug delivery systems, including for cutaneous applications. Cyclodextrins (CDs) have been utilised to enhance the nanogels’ loading ability towards poorly soluble drugs and promote/sustain drug release. However, formation of CD-based [...] Read more.
Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective drug delivery systems, including for cutaneous applications. Cyclodextrins (CDs) have been utilised to enhance the nanogels’ loading ability towards poorly soluble drugs and promote/sustain drug release. However, formation of CD-based nanogels requires the use of specially modified CDs, or of crosslinking agents. The aim of this work was to develop a CD-based nanogel to improve the cutaneous delivery of ibuprofen by using the soluble β-cyclodextrin/epichlorohydrin polymer (EPIβCD) without adding any potentially toxic crosslinker. The use of EPIβCD enabled increasing ibuprofen loading due to its complexing/solubilizing power towards the poorly soluble drug and prolonging drug release over time due to the nanogel formation. DLS analysis proved that EPIβCD allowed the formation of nanostructures ranging from 60 up to 400 nm, depending on the gelling agent type and the gel preparation method. EPIβCD replacement with monomeric HPβCD did not lead in any case to nanogel formation. Permeation experiments using skin-simulating artificial membranes proved that the EPIβCD-based nanogel enhanced ibuprofen solubility and release, increasing its permeation rate up to 3.5 times, compared to a reference formulation without CD and to some commercial gel formulations, and also assured a sustained release. Moreover, EPIβCD replacement with HPβCD led to a marked increase in drug solubility and initial release rate, but did not provide a prolonged release due to the lack of a nano-matrix structure controlling drug diffusion. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications)
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Review

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25 pages, 1816 KiB  
Review
Lipid-Based Delivery Systems for Flavonoids and Flavonolignans: Liposomes, Nanoemulsions, and Solid Lipid Nanoparticles
by Shahla Ranjbar, Abbasali Emamjomeh, Fatemeh Sharifi, Atefeh Zarepour, Kian Aghaabbasi, Ali Dehshahri, Azadeh Mohammadi Sepahvand, Ali Zarrabi, Hamid Beyzaei, Mohammad Mehdi Zahedi and Reza Mohammadinejad
Pharmaceutics 2023, 15(7), 1944; https://doi.org/10.3390/pharmaceutics15071944 - 14 Jul 2023
Cited by 3 | Viewed by 2568
Abstract
Herbal chemicals with a long history in medicine have attracted a lot of attention. Flavonolignans and flavonoids are considered as two classes of the above-mentioned compounds with different functional groups which exhibit several therapeutic capabilities such as antimicrobial, anti-inflammatory, antioxidant, antidiabetic, and anticancer [...] Read more.
Herbal chemicals with a long history in medicine have attracted a lot of attention. Flavonolignans and flavonoids are considered as two classes of the above-mentioned compounds with different functional groups which exhibit several therapeutic capabilities such as antimicrobial, anti-inflammatory, antioxidant, antidiabetic, and anticancer activities. Based on the studies, high hydrophobic properties of the aforementioned compounds limit their bioavailability inside the human body and restrict their wide application. Nanoscale formulations such as solid lipid nanoparticles, liposomes, and other types of lipid-based delivery systems have been introduced to overcome the above-mentioned challenges. This approach allows the aforementioned hydrophobic therapeutic compounds to be encapsulated between hydrophobic structures, resulting in improving their bioavailability. The above-mentioned enhanced delivery system improves delivery to the targeted sites and reduces the daily required dosage. Lowering the required daily dose improves the performance of the drug by diminishing its side effects on non-targeted tissues. The present study aims to highlight the recent improvements in implementing lipid-based nanocarriers to deliver flavonolignans and flavonoids. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology-Based Approaches for Pharmaceutical Applications)
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