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Potent synthetic drugs, as well as biomolecules extracted from plants, have been investigated for their selectivity toward cancer cells. The main limitation in cancer treatment is the ability to bring such molecules within each single cancer cell, which requires accumulation in the peritumoral region followed by homogeneous spreading within the entire tissue. In the last decades, nanotechnology has emerged as a powerful tool due to its ability to protect the drug during blood circulation and allow enhanced accumulation around the leaky regions of the tumor vasculature. However, the ideal size for accumulation of around 100 nm is too large for effective penetration into the dense collagen matrix. Therefore, we propose a multistage system based on graphene oxide nanosheet-based quantum dots (GOQDs) with dimensions that are 12 nm, functionalized with hyaluronic acid (GOQDs-HA), and deposited using the layer-by-layer technique onto an oil-in-water nanoemulsion (O/W NE) template that is around 100 nm in size, previously stabilized by a biodegradable polymer, chitosan. The choice of a biodegradable core for the nanocarrier is to degrade once inside the tumor, thus promoting the release of smaller compounds, GOQDs-HA, carrying the adsorbed anticancer compound, which in this work is represented by curcumin as a model bioactive anticancer molecule. Additionally, modification with HA aims to promote active targeting of stromal and cancer cells. Cell uptake experiments and preliminary penetration experiments in three-dimensional microtissues were performed to assess the proposed multistage nanocarrier. [ABSTRACT FROM AUTHOR]

Podophyllotoxin is a naturally occurring cyclolignan isolated from rhizomes of Podophyllum sp. In the clinic, it is used mainly as an antiviral; however, its antitumor activity is even more interesting. While podophyllotoxin possesses severe side effects that limit its development as an anticancer agent, nevertheless, it has become a good lead compound for the synthesis of derivatives with fewer side effects and better selectivity. Several examples, such as etoposide, highlight the potential of this natural product for chemomodulation in the search for new antitumor agents. This review focuses on the recent chemical modifications (2017–mid-2023) of the podophyllotoxin skeleton performed mainly at the C-ring (but also at the lactone D-ring and at the trimethoxyphenyl E-ring) together with their biological properties. Special emphasis is placed on hybrids or conjugates with other natural products (either primary or secondary metabolites) and other molecules (heterocycles, benzoheterocycles, synthetic drugs, and other moieties) that contribute to improved podophyllotoxin bioactivity. In fact, hybridization has been a good strategy to design podophyllotoxin derivatives with enhanced bioactivity. The way in which the two components are joined (directly or through spacers) was also considered for the organization of this review. This comprehensive perspective is presented with the aim of guiding the medicinal chemistry community in the design of new podophyllotoxin-based drugs with improved anticancer properties. [ABSTRACT FROM AUTHOR]

The short shelf life of platelet concentrates (PC) of up to 5–7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. Engineered nanocarriers functionalized with platelet membranes have shown excellent targeting abilities for tumor cells owing to their platelet membrane proteins. Nevertheless, synthetic drug delivery strategies have significant drawbacks that platelet-derived extracellular vesicles (pEV) can overcome. We investigated, for the first time, the use of pEV as a carrier of the anti-breast cancer drug paclitaxel, considering it as an appealing alternative to improve the therapeutic potential of expired PC. The pEV released during PC storage showed a typical EV size distribution profile (100–300 nm) with a cup-shaped morphology. Paclitaxel-loaded pEV showed significant anti-cancer effects in vitro, as demonstrated by their anti-migratory (>30%), anti-angiogenic (>30%), and anti-invasive (>70%) properties in distinct cells found in the breast tumor microenvironment. We provide evidence for a novel application for expired PC by suggesting that the field of tumor treatment research may be broadened by the use of natural carriers. [ABSTRACT FROM AUTHOR]

Microwave-assisted synthetic methods have emerged as a popular technique for surface modification and the functionalization of multi-walled carbon nanotubes (MWCNTs) for diverse drug delivery applications. Microwave-induced functionalization of MWCNTs provides a high functionalization and requires less time than conventional techniques. Microwave methods are simple, fast, and effective for the covalent and noncovalent conjugation of MWCNTs with various biomolecules and polymers. The present review focuses on the synthetic and drug delivery applications of microwave irradiation techniques (MITs) for the functionalization of MWCNTs, using amino acids and other molecular frameworks containing amino groups, vitamins, proteins, epoxy moieties, metal nanoparticles, and polymers. [ABSTRACT FROM AUTHOR]

The purpose of this review is to provide verified data on the current knowledge acquired in preclinical and clinical studies regarding topically used herbal products and their active constituents (formulations and dressings) with diabetic wound healing activity. Moreover, herbal products and their active constituents used for diabetic wound infections, and various cellular and molecular mechanisms of their actions will also be described. The electronic databases were searched for articles published from 2012 to 2022. Publications with oral or systemic administration of herbal products in diabetic wound healing, published before 2012, available only as an abstract, or in languages other than English were excluded from the study. The 59 articles comparing topically used herbal products in diabetic wound healing treatment versus control treatments (placebo or active therapy) were selected. Herbal products through different mechanisms of action, including antimicrobial, anti-inflammatory, antioxidant activity, stimulation of angiogenesis, production of cytokines and growth factors, keratinocytes, and fibroblast migration and proliferation may be considered as an important support during conventional therapy or even as a substitute for synthetic drugs used for diabetic wound treatment. [ABSTRACT FROM AUTHOR]

The use of natural compounds is becoming increasingly popular among patients, and there is a renewed interest among scientists in nature-based bioactive agents. Traditionally, herbal drugs can be taken directly in the form of teas/decoctions/infusions or as standardized extracts. However, the disadvantages of natural compounds, especially essential oils, are their instability, limited bioavailability, volatility, and often irritant/allergenic potential. However, these active substances can be stabilized by encapsulation and administered in the form of nanoparticles. This brief overview summarizes the latest results of the application of nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers used as drug delivery systems of herbal essential oils or used directly for their individual secondary metabolites applicable in cancer therapy. Although the discussed bioactive agents are not typical compounds used as anticancer agents, after inclusion into the aforesaid formulations improving their stability and bioavailability and/or therapeutic profile, they indicated anti-tumor activity and became interesting agents with cancer treatment potential. In addition, co-encapsulation of essential oils with synthetic anticancer drugs into nanoformulations with the aim to achieve synergistic effect in chemotherapy is discussed. [ABSTRACT FROM AUTHOR]

Diabetes is a chronic disease that leads to abnormal carbohydrate digestion and hyperglycemia. The long-term use of marketed drugs results in secondary infections and side effects that demand safe and natural substitutes for synthetic drugs. The objective of this study is to evaluate the antidiabetic potential of compounds from the leaves of Tradescantia pallida. Thirteen phenolic compounds were identified from the ethyl acetate fraction of leaves of Tradescantia pallida using liquid chromatography-mass spectrometry. The compounds were then studied for the type of interactions between polyphenols and human α-glucosidase protein using molecular docking analysis. Prime Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) calculations were performed to measure the binding free energies responsible for the formation of ligand–protein complexes. The compounds were further investigated for the thermodynamic constraints under a specified biological environment using molecular dynamic simulations. The flexibility of the ligand–protein systems was verified by Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and molecular interactions. The results authenticated the antidiabetic potential of polyphenols identified from the leaves of Tradescantia pallida. Our investigations could be helpful in the design of safe antidiabetic agents, but further in vitro and in vivo investigations are required. [ABSTRACT FROM AUTHOR]

Tacrolimus is an immunosuppressive calcineurin inhibitor used to prevent rejection in allogeneic organ transplant recipients, such as kidney, liver, heart or lung. It is metabolized in the liver, involving the cytochrome P450 (CYP3A4) isoform CYP3A4, and is characterized by a narrow therapeutic window, dose-dependent toxicity and high inter-individual and intra-individual variability. In view of the abovementioned facts, the aim of the study is to present selected interactions between tacrolimus and the commonly used dietary supplements, herbs and food. The review was based on the available scientific literature found in the PubMed, Scopus and Cochrane databases. An increase in the serum concentration of tacrolimus can be caused by CYP3A4 inhibitors, such as grapefruit, pomelo, clementine, pomegranate, ginger and turmeric, revealing the side effects of this drug, particularly nephrotoxicity. In contrast, CYP3A4 inducers, such as St. John's Wort, may result in a lack of therapeutic effect by reducing the drug concentration. Additionally, the use of Panax ginseng, green tea, Schisandra sphenanthera and melatonin in patients receiving tacrolimus is highly controversial. Therefore, since alternative medicine constitutes an attractive treatment option for patients, modern healthcare should emphasize the potential interactions between herbal medicines and synthetic drugs. In fact, each drug or herbal supplement should be reported by the patient to the physician (concordance) if it is taken in the course of immunosuppressive therapy, since it may affect the pharmacokinetic and pharmacodynamic parameters of other preparations. [ABSTRACT FROM AUTHOR]

Various active compounds isolated from natural sources exhibit remarkable benefits, making them attractive for pharmaceutical and biomedical applications, such as antioxidant, antimicrobial, and anti-inflammatory activities, which contribute to the treatment of cardiovascular diseases, neurodegenerative disorders, various types of cancer, diabetes, and obesity. However, their major drawbacks are their reactivity, instability, relatively poor water solubility, and consequently low bioavailability. Synthetic drugs often face similar challenges associated with inadequate solubility or burst release in gastrointestinal media, despite being otherwise a safe and effective option for the treatment of numerous diseases. Therefore, drug-eluting pharmaceutical formulations have been of great importance over the years in efforts to improve the bioavailability of active compounds by increasing their solubility and achieving their controlled release in body media. This review highlights the success of the fabrication of micro- and nanoformulations using environmentally friendly supercritical fluid technologies for the processing and incorporation of active compounds. Several novel approaches, namely micronization to produce micro- and nano-sized particles, supercritical drying to produce aerogels, supercritical foaming, and supercritical solvent impregnation, are described in detail, along with the currently available drug delivery data for these formulations. [ABSTRACT FROM AUTHOR]

Application of modern delivery techniques to natural bioactive products improves their permeability, bioavailability, and therapeutic efficacy. Many natural products have desirable biological properties applicable to wound healing but are limited by their inability to cross the stratum corneum to access the wound. Over the past two decades, modern systems such as microneedles, lipid-based vesicles, hydrogels, composite dressings, and responsive formulations have been applied to natural products such as curcumin or aloe vera to improve their delivery and efficacy. This article reviews which natural products and techniques have been formulated together in the past two decades and the success of these applications for wound healing. Many cultures prefer natural-product-based traditional therapies which are often cheaper and more available than their synthetic counterparts. Improving natural products' effect can provide novel wound-healing therapies for those who trust traditional compounds over synthetic drugs to reduce medical inequalities. [ABSTRACT FROM AUTHOR]

The continuous technological advancement of nanomedicine has enabled the development of novel vehicles for the effective delivery of therapeutic substances. Synthetic drug delivery systems are nano-sized carriers made from various materials that can be designed to deliver therapeutic cargoes to cells or tissues. However, rapid clearance by the immune system and the poor targeting profile of synthetic drug delivery systems are examples of the pressing obstacles faced in nanomedicine, which have directed the field toward the development of alternative strategies. Extracellular vesicles (EVs) are nanoscale particles enclosed by a protein-rich lipid bilayer; they are released by cells and are considered to be important mediators of intercellular communication. Owing to their natural composition, EVs have been suggested to exhibit good biocompatibility and to possess homing properties to specific cell types. Combining EVs with synthetic nanoparticles by defined hybridization steps gives rise to a novel potential drug delivery tool, i.e., EV-based hybrid systems. These novel therapeutic vehicles exhibit potential advantageous features as compared to synthetic drug delivery systems such as enhanced cellular uptake and cargo delivery, immuno-evasive properties, capability of crossing biological barriers, and tissue targeting profile. Here, we provide an overview of the various strategies practiced to produce EV-based hybrid systems and elucidate those advantageous features obtained by synthetic drug delivery systems upon hybridization with EVs. [ABSTRACT FROM AUTHOR]

In the present study, luteolin (LT)-loaded nanosized vesicles (LT-NVs) were prepared by a solvent evaporation–hydration method using phospholipid and edge activator. The formulation was optimized using three factors at a three-level Box–Behnken design. The formulated LT-NVs were prepared using the three independent variables phospholipid (A), edge activator (B) and sonication time (C). The effect of used variables was assessed on the vesicle size (Y1) and encapsulation efficiency (Y2). The selection of optimum composition (LT-NVopt) was based on the point prediction method of the software. The prepared LT-NVopt showed the particle size of 189.92 ± 3.25 nm with an encapsulation efficiency of 92.43 ± 4.12% with PDI and zeta potential value of 0.32 and −21 mV, respectively. The formulation LT-NVopt was further converted into Carbopol 934 gel (1% w/v) to enhance skin retention. LT-NVoptG was further characterized for viscosity, spreadability, drug content, drug release, drug permeation and antioxidant, antimicrobial and cytotoxicity assessment. The evaluation result revealed optimum pH, viscosity, spreadability and good drug content. There was enhanced LT release (60.81 ± 2.87%), as well as LT permeation (128.21 ± 3.56 µg/cm2/h), which was found in comparison to the pure LT. The antioxidant and antimicrobial study results revealed significantly (p ˂ 0.05) better antioxidant potential and antimicrobial activity against the tested organisms. Finally, the samples were evaluated for cytotoxicity assessment using skin cancer cell line and results revealed a significant difference in the viability % at the tested concentration. LT-NVoptG showed a significantly lower IC50 value than the pure LT. From the study, it can be concluded that the prepared LT-NVoptG was found to be an alternative to the synthetic drug as well as conventional delivery systems. [ABSTRACT FROM AUTHOR]

The current treatment of depression involves antidepressant synthetic drugs that have a variety of side effects. In searching for alternatives, natural compounds could represent a solution, as many studies reported that such compounds modulate the nervous system and exhibit antidepressant effects. We used bioinformatics methods to predict the antidepressant effect of ten natural compounds with neuroleptic activity, reported in the literature. For all compounds we computed their drug-likeness, absorption, distribution, metabolism, excretion (ADME), and toxicity profiles. Their antidepressant and neuroleptic activities were predicted by 3D-ALMOND-QSAR models built by considering three important targets, namely serotonin transporter (SERT), 5-hydroxytryptamine receptor 1A (5-HT1A), and dopamine D2 receptor. For our QSAR models we have used the following molecular descriptors: hydrophobicity, electrostatic, and hydrogen bond donor/acceptor. Our results showed that all compounds present drug-likeness features as well as promising ADME features and no toxicity. Most compounds appear to modulate SERT, and fewer appear as ligands for 5-HT1A and D2 receptors. From our prediction, linalyl acetate appears as the only ligand for all three targets, neryl acetate appears as a ligand for SERT and D2 receptors, while 1,8-cineole appears as a ligand for 5-HT1A and D2 receptors. [ABSTRACT FROM AUTHOR]

Infections due to HSV-1 affect many people all over the world. To counteract this pathology, usually characterized by perioral sores or by less frequent serious symptoms including keratitis, synthetic antiviral drugs are employed, such as acyclovir, often resulting in resistant viral strains under long-term use. Many plant-derived compounds, such as mangiferin and quercetin, have demonstrated antiviral potentials. In this study, smart semisolid forms based on phosphatidylcholine and Pluronic were investigated as delivery systems to administer mangiferin on skin and mucosae affected by HSV-1 infection. Particularly, lecithin organogels, Pluronic gel, and Pluronic lecithin organogels were formulated and characterized. After the selection of gel compositions, physical aspects, such as rheological behavior, spreadability, leakage, and adhesion were evaluated, suggesting a scarce suitability of the lecithin organogel for topical administration. Mangiferin was efficiently included in all type of gels. An in vitro study based on the Franz cell enabled us to find evidence of the gel capability to control drug diffusion, especially in the case of Pluronic organogel, while an in vivo study conducted on human volunteers demonstrated the safeness of all of the gels after cutaneous administration. Furthermore, a plaque reduction assay demonstrated the virucidal effect of mangiferin loaded in a Pluronic gel and a Pluronic lecithin organogel against the HSV-1 KOS strain. [ABSTRACT FROM AUTHOR]

Respiratory viral infections have been a leading cause of morbidity and mortality worldwide. Despite massive advancements in the virology field, no specific treatment exists for most respiratory viral infections. Approved therapies against respiratory viruses rely almost exclusively on synthetic drugs that have potential side effects, restricting their use. This review aims to present natural marine sulfated polysaccharides possessing promising antiviral activity against respiratory viruses that could be a safe alternative to synthetic broad-spectrum antiviral drugs. The antiviral properties of marine sulfated polysaccharides are presented according to their mechanism of action on different types and strains of respiratory viruses, and the potential limits of their use are discussed. [ABSTRACT FROM AUTHOR]