New Trends in Therapy: From Natural Products to Nanomedicine

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

Deadline for manuscript submissions: closed (10 December 2021) | Viewed by 21688

Special Issue Editors


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Guest Editor
Institute of Nutrition and Food Technology “José Mataix Verdú”, Department of Physiology, Biomedical Research Center, University of Granada, Avda del Conocimiento sn., 18100 Armilla, Granada, Spain
Interests: metals; nanoparticles; micronutrients
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Biomedical Research Centre, Institute of Nutrition and Food Technology, Department of Physiology, Faculty of Pharmacy, University of Granada, 18016 Granada, Spain
Interests: nanomedicine; food technology; nutrition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, new approaches for the treatment of diseases are gaining attention in the biomedical sciences for the development of secure and personalized medicine. This requires research based on close collaboration between different scientific fields. At present, the discovery of new therapeutic tools could be mediated by different disciplines; therapies based on nanoparticles have related promising advances through some approaches like drug delivery, gene therapy, or hyperthermia. On the other hand, natural products (like medicinal plants) and their active ingredients play an important role in the discovery of new drugs and innovative mechanisms of action. Furthermore, molecules derived from manufacturing/food processing are yielding promising results that could be applied to expand new knowledge in pharmaceutics/nutraceutics.

This Special Issue aims to contribute original articles and reviews (e.g., systematic reviews) to the identification of new potential agents in therapy (alone or in combination) with anyone origin and scientific discipline.

Prof. Dr. Juan Llopis
Prof. Dr. Cristina Sánchez González
Dr. Lorenzo Rivas García
Guest Editors

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Keywords

  • nanoparticles
  • gene/drug delivery
  • plant based extract
  • natural products
  • medicinal plants
  • antioxidants
  • organometallic compounds
  • in vivo/in vitro assays
  • redox biology
  • cancer therapies
  • combination therapy
  • food technology

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Published Papers (6 papers)

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Research

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21 pages, 2979 KiB  
Article
Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci
by Anna Maria Schito, Debora Caviglia, Gabriella Piatti, Alessia Zorzoli, Danilo Marimpietri, Guendalina Zuccari, Gian Carlo Schito and Silvana Alfei
Pharmaceutics 2021, 13(11), 1976; https://doi.org/10.3390/pharmaceutics13111976 - 21 Nov 2021
Cited by 10 | Viewed by 2311
Abstract
Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its [...] Read more.
Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the Enterococcus genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5–4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against E. faecium, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD50 (96.4 µM) and selectivity indices, which were in the range 22.4–192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections. Full article
(This article belongs to the Special Issue New Trends in Therapy: From Natural Products to Nanomedicine)
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13 pages, 2227 KiB  
Article
Cellular Toxicity Mechanisms and the Role of Autophagy in Pt(IV) Prodrug-Loaded Ultrasmall Iron Oxide Nanoparticles Used for Enhanced Drug Delivery
by L. Gutiérrez-Romero, L. Rivas-García, C. Sánchez-González, J. Llopis, E. Blanco and M. Montes-Bayón
Pharmaceutics 2021, 13(10), 1730; https://doi.org/10.3390/pharmaceutics13101730 - 19 Oct 2021
Cited by 5 | Viewed by 2520
Abstract
Ultrasmall iron oxide nanoparticles (<10 nm) were loaded with cis-diamminetetrachloroplatinum (IV), a cisplatin (II) prodrug, and used as an efficient nanodelivery system in cell models. To gain further insight into their behavior in ovarian cancer cells, the level of cellular incorporation as well [...] Read more.
Ultrasmall iron oxide nanoparticles (<10 nm) were loaded with cis-diamminetetrachloroplatinum (IV), a cisplatin (II) prodrug, and used as an efficient nanodelivery system in cell models. To gain further insight into their behavior in ovarian cancer cells, the level of cellular incorporation as well as the platination of mitochondrial and nuclear DNA were measured using inductively coupled plasma mass spectrometry (ICP-MS) strategies. Quantitative Pt results revealed that after 24 h exposure to 20 µM Pt in the form of the Pt(IV)-loaded nanoparticles, approximately 10% of the incorporated Pt was associated with nuclear DNA. This concentration increased up to 60% when cells were left to stand in drug-free media for 3 h. These results indicated that the intracellular reducing conditions permitted the slow release of cisplatin (II) from the cisplatin (IV)-loaded nanoparticles. Similar results were obtained for the platination of mitochondrial DNA, which reached levels up to 17,400 ± 75 ng Pt/ mg DNA when cells were left in drug-free media for 3 h, proving that this organelle was also a target for the action of the released cisplatin (II). The time-dependent formation of Pt-DNA adducts could be correlated with the time-dependent decrease in cell viability. Such a decrease in cell viability was correlated with the induction of apoptosis as the main route of cell death. The formation of autophagosomes, although observed upon exposure in treated cells, does not seem to have played an important role as a means for cells to overcome nanoparticles’ toxicity. Thus, the designed nanosystem demonstrated high cellular penetration and the “in situ” production of the intracellularly active cisplatin (II), which is able to induce cell death, in a sustained manner. Full article
(This article belongs to the Special Issue New Trends in Therapy: From Natural Products to Nanomedicine)
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13 pages, 1021 KiB  
Article
Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats
by Miguel Navarro-Alarcón, Fernando Gil-Hernández, Cristina Sánchez-González, Juan Llopis, Marina Villalón-Mir, Pablo Olmedo, Pablo Alarcón-Guijo, Diego Salagre, Lorena Gaona, Mario Paredes and Ahmad Agil
Pharmaceutics 2021, 13(10), 1535; https://doi.org/10.3390/pharmaceutics13101535 - 22 Sep 2021
Viewed by 1860
Abstract
Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal (perirenal, perigonadal, and omentum) and subcutaneous lumbar [...] Read more.
Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal (perirenal, perigonadal, and omentum) and subcutaneous lumbar white adipose tissues (IWAT and SWAT, respectively). Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight/day) or vehicle for 6 weeks. Zn and Cu concentrations were not significantly influenced by diabesity in the analyzed tissues (p > 0.05), with the exception of Zn in liver. In skeletal muscle Zn and Cu, and in perirenal WAT, only Zn levels increased significantly with melatonin supplementation in ZDF rats (p < 0.05). This cytoplasmic Zn enhancement would be probably associated with the upregulation of several Zn influx membrane transporters (Zips) and could explain the amelioration in the glycaemia and insulinaemia by upregulating the Akt and downregulating the inhibitor PTP1B, in obese and diabetic conditions. Enhanced Zn and Cu levels in muscle cells could be related to the reported antioxidant melatonin activity exerted by increasing the Zn, Cu-SOD, and extracellular Cu-SOD activity. In conclusion, melatonin, by increasing the muscle levels of Zn and Cu, joined with our previously reported findings improves glycaemia, insulinaemia, and oxidative stress in this diabesity animal model. Full article
(This article belongs to the Special Issue New Trends in Therapy: From Natural Products to Nanomedicine)
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29 pages, 4022 KiB  
Article
A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy
by Cristina Ioana Barbălată, Alina Silvia Porfire, Alina Sesarman, Valentin-Florian Rauca, Manuela Banciu, Dana Muntean, Rareș Știufiuc, Alin Moldovan, Cristian Moldovan and Ioan Tomuță
Pharmaceutics 2021, 13(10), 1526; https://doi.org/10.3390/pharmaceutics13101526 - 22 Sep 2021
Cited by 18 | Viewed by 2921
Abstract
An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing [...] Read more.
An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing the Quality by Design (QbD) concept, as a means to enhance the antiproliferative effect of the co-formulation on C26 murine colon cancer cells co-cultured with macrophages. It is known that the quality profile of liposomes is dependent on the critical quality attributes (CQAs) of liposomes (drug entrapped concentration, encapsulation efficiency, size, zeta potential, and drug release profile), which are, in turn, directly influenced by various formulation factors and processing parameters. By using the design of experiments, it was possible to outline the increased variability of CQAs in relation to formulation factors and identify by means of statistical analysis the material attributes that are critical (phospholipids, DOX and SIM concentration) for the quality of the co-formulation. The in vitro studies performed on a murine colon cancer cell line highlighted the importance of delivering the optimal drug ratio at the target site, since the balance antiproliferative vs. pro-proliferative effects can easily be shifted when the molar ratio between DOX and SIM changes. Full article
(This article belongs to the Special Issue New Trends in Therapy: From Natural Products to Nanomedicine)
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Review

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27 pages, 1436 KiB  
Review
Artemisinin-Type Drugs in Tumor Cell Death: Mechanisms, Combination Treatment with Biologics and Nanoparticle Delivery
by Xinyu Zhou, Fengzhi Suo, Kristina Haslinger and Wim J. Quax
Pharmaceutics 2022, 14(2), 395; https://doi.org/10.3390/pharmaceutics14020395 - 10 Feb 2022
Cited by 10 | Viewed by 4397
Abstract
Artemisinin, the most famous anti-malaria drug initially extracted from Artemisia annua L., also exhibits anti-tumor properties in vivo and in vitro. To improve its solubility and bioavailability, multiple derivatives have been synthesized. However, to reveal the anti-tumor mechanism and improve the efficacy of [...] Read more.
Artemisinin, the most famous anti-malaria drug initially extracted from Artemisia annua L., also exhibits anti-tumor properties in vivo and in vitro. To improve its solubility and bioavailability, multiple derivatives have been synthesized. However, to reveal the anti-tumor mechanism and improve the efficacy of these artemisinin-type drugs, studies have been conducted in recent years. In this review, we first provide an overview of the effect of artemisinin-type drugs on the regulated cell death pathways, which may uncover novel therapeutic approaches. Then, to overcome the shortcomings of artemisinin-type drugs, we summarize the recent advances in two different therapeutic approaches, namely the combination therapy with biologics influencing regulated cell death, and the use of nanocarriers as drug delivery systems. For the former approach, we discuss the superiority of combination treatments compared to monotherapy in tumor cells based on their effects on regulated cell death. For the latter approach, we give a systematic overview of nanocarrier design principles used to deliver artemisinin-type drugs, including inorganic-based nanoparticles, liposomes, micelles, polymer-based nanoparticles, carbon-based nanoparticles, nanostructured lipid carriers and niosomes. Both approaches have yielded promising findings in vitro and in vivo, providing a strong scientific basis for further study and upcoming clinical trials. Full article
(This article belongs to the Special Issue New Trends in Therapy: From Natural Products to Nanomedicine)
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23 pages, 3411 KiB  
Review
Advances in Cancer Therapeutics: Conventional Thermal Therapy to Nanotechnology-Based Photothermal Therapy
by Sangeeta Kumari, Nilesh Sharma and Shivendra V. Sahi
Pharmaceutics 2021, 13(8), 1174; https://doi.org/10.3390/pharmaceutics13081174 - 30 Jul 2021
Cited by 51 | Viewed by 6403
Abstract
In this review, advancement in cancer therapy that shows a transition from conventional thermal therapies to laser-based photothermal therapies is discussed. Laser-based photothermal therapies are gaining popularity in cancer therapeutics due to their overall outcomes. In photothermal therapy, light is converted into heat [...] Read more.
In this review, advancement in cancer therapy that shows a transition from conventional thermal therapies to laser-based photothermal therapies is discussed. Laser-based photothermal therapies are gaining popularity in cancer therapeutics due to their overall outcomes. In photothermal therapy, light is converted into heat to destruct the various types of cancerous growth. The role of nanoparticles as a photothermal agent is emphasized in this review article. Magnetic, as well as non-magnetic, nanoparticles have been effectively used in the photothermal-based cancer therapies. The discussion includes a critical appraisal of in vitro and in vivo, as well as the latest clinical studies completed in this area. Plausible evidence suggests that photothermal therapy is a promising avenue in the treatment of cancer. Full article
(This article belongs to the Special Issue New Trends in Therapy: From Natural Products to Nanomedicine)
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