Polymer-Based Nanoparticles as Drug Delivery Systems for Purines of Established Importance in Medicine.

Many purine derivatives are active pharmaceutical ingredients of significant importance in the therapy of autoimmune diseases, cancers, and viral infections. In many cases, their medical use is limited due to unfavorable physicochemical and pharmacokinetic properties. These problems can be overcome by the preparation of the prodrugs of purines or by combining these compounds with nanoparticles. Herein, we aim to review the scientific progress and perspectives for polymer-based nanoparticles as drug delivery systems for purines. Polymeric nanoparticles turned out to have the potential to augment antiviral and antiproliferative effects of purine derivatives by specific binding to receptors (ASGR1-liver, macrophage mannose receptor), increase in drug retention (in eye, intestines, and vagina), and permeation (intranasal to brain delivery, PEPT1 transport of acyclovir). The most significant achievements of polymer-based nanoparticles as drug delivery systems for purines were found for tenofovir disoproxil in protection against HIV, for acyclovir against HSV, for 6-mercaptopurine in prolongation of mice ALL model life, as well as for 6-thioguanine for increased efficacy of adoptively transferred T cells. Moreover, nanocarriers were able to diminish the toxic effects of acyclovir, didanosine, cladribine, tenofovir, 6-mercaptopurine, and 6-thioguanine.

Nanotechnology for Dentistry: Prospects and Applications.

In the XXI century, application of nanostructures in oral medicine has become common. In oral medicine, using nanostructures for the treatment of dental caries constitutes a great challenge. There are extensive studies on the implementation of nanomaterials to dental composites in order to improve their properties, e.g., their adhesive strength. Moreover, nanostructures are helpful in dental implant applications as well as in maxillofacial surgery for accelerated healing, promoting osseointegration, and others. Dental personal care products are an important part of oral medicine where nanomaterials are increasingly used, e.g., toothpaste for hypersensitivity. Nowadays, nanoparticles such as macrocycles are used in different formulations for early cancer diagnosis in the oral area. Cancer of the oral cavity-human squamous carcinoma-is the sixth leading cause of death. Detection in the early stage offers the best chance at total cure. Along with diagnosis, macrocycles are used for photodynamic mechanism-based treatments, which possess many advantages, such as protecting healthy tissues and producing good cosmetic results. Application of nanostructures in medicine carries potential risks, like long-term influence of toxicity on body, which need to be studied further. The introduction and development of nanotechnologies and nanomaterials are no longer part of a hypothetical future, but an increasingly important element of today's medicine.

Metal Nanoparticle-Flavonoid Connections: Synthesis, Physicochemical and Biological Properties, as Well as Potential Applications in Medicine.

Flavonoids are polyphenolic compounds widely occurring throughout the plant kingdom. They are biologically active and have many medical applications. Flavonoids reveal chemopreventive, anticarcinogenic, and antioxidant properties, as well as being able to modulate the immune system response and inhibit inflammation, angiogenesis, and metastasis. Polyphenols are also believed to reverse multidrug resistance via various mechanisms, induce apoptosis, and activate cell death signals in tumor cells by modulating cell signaling pathways. The main limitation to the broader usage of flavonoids is their low solubility, poor absorption, and rapid metabolism. To tackle this, the combining of flavonoids with nanocarriers could improve their bioavailability and create systems of wider functionalities. Recently, interest in hybrid materials based on combinations of metal nanoparticles with flavonoids has increased due to their unique physicochemical and biological properties, including improved selectivity toward target sites. In addition, flavonoids have further utilities, even in the initial step of preparation of metal nanomaterials. The review offers knowledge on multiple possibilities of the synthesis of flavonoid-metal nanoparticle conjugates, as well as presents some of their features such as size, shape, surface charge, and stability. The flavonoid-metal nanoparticles are also discussed regarding their biological properties and potential medical applications.

Gallic Acid-Functionalized, TiO2-Based Nanomaterial-Preparation, Physicochemical and Biological Properties.

Wound healing and skin tissue regeneration remain the most critical challenges faced by medical professionals. Titanium(IV) oxide-based materials were proposed as components of pharmaceutical formulations for the treatment of difficult-to-heal wounds and unsightly scarring. A gallic acid-functionalized TiO2 nanomaterial (TiO2-GA) was obtained using the self-assembly technique and characterized using the following methods: scanning electron microscopy (SEM), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), X-ray powder diffraction (XRPD), infrared spectroscopy (IR), Raman spectroscopy and thermogravimetry (TG). Additionally, physicochemical and biological tests (DPPH assay, Microtox® acute toxicity test, MTT assay) were performed to assess antioxidant properties as well as to determine the cytotoxicity of the novel material against eukaryotic (MRC-5 pd19 fibroblasts) and prokaryotic (Staphylococcus aureus, Escherichia coli, Candida albicans, Aliivibrio fischeri) cells. To determine the photocytotoxicity of the material, specific tests were carried out with and without exposure to visible light lamps (425 nm). Following the results, the TiO2-GA material could be considered an additive to dressings and rinsing suspensions for the treatment of difficult-to-heal wounds that are at risk of bacterial infections.

Excited State and Reactive Oxygen Species against Cancer and Pathogens: A Review on Sonodynamic and Sono-Photodynamic Therapy.

Photodynamic and sonodynamic therapy are therapies having great potential in the treatment of bacterial infections and cancer. Their background is associated with photo- and sonosensitizers - substances that can be excited when exposed to light or ultrasound. These sensitizers belong to a various groups of compound, including porphyrins, porphyrazines, and phthalocyanines. Releasing the energy when returning to the ground state can occur in the manner of transferring it to oxygen molecules, leading to reactive oxygen species able to disrupt membranes of bacterial and cancer cells, leaving the organism's cells unaffected. In recent years, the number of reports on numerous sensitizers being effective has been constantly growing. Therefore, the development of this field may prove beneficial for dealing with cancer and microbes. This review describes the development of photodynamic and sonodynamic therapy, as well as their combination, with emphasis on sonodynamic therapy and its potential in the treatment of cancer and bacterial infections.

Occurrence and dietary risk of bisphenols and parabens in raw and processed cow's milk.

Raw cow's milk collected from farmers and processed cow's milk purchased from local grocery stores were analysed for the presence of six bisphenols (bisphenol A, bisphenol S, bisphenol F, bisphenol AF, bisphenol B, and bisphenol E) and five parabens (methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben). The analytes were determined in their unconjugated form and (after enzymatic deconjugation) as the sum of conjugated and unconjugated compounds. The results show the presence of bisphenols mainly in the processed milk bought in stores while parabens were found in all samples of both raw and processed cow's milk. The average concentration of bisphenol A found in milk from cartons (0.87 ng mL-1) was greater than in milk from plastic bottles (0.35 ng mL-1). No such difference was found for parabens. Also, no considerable difference between the content of conjugated and total bisphenols and parabens was found except for ethylparaben. The determined compounds were always found below 2.0 ng mL-1 and calculations of the hazard quotients and the hazard index have shown that consumption of such milk is safe.

Photosensitizers Mediated Photodynamic Inactivation against Fungi.

Superficial and systemic fungal infections are essential problems for the modern health care system. One of the challenges is the growing resistance of fungi to classic antifungals and the constantly increasing cost of therapy. These factors force the scientific world to intensify the search for alternative and more effective methods of treatment. This paper presents an overview of new fungal inactivation methods using Photodynamic Antimicrobial Chemotherapy (PACT). The results of research on compounds from the groups of phenothiazines, xanthanes, porphyrins, chlorins, porphyrazines, and phthalocyanines are presented. An intensive search for a photosensitizer with excellent properties is currently underway. The formulation based on the existing ones is also developed by combining them with nanoparticles and common antifungal therapy. Numerous studies indicate that fungi do not form any specific defense mechanism against PACT, which deems it a promising therapeutic alternative.

In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine.

Azulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such as Matricaria chamomilla, Artemisia absinthium, Achillea millefolium, and Lactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies. Herein, the applications of azulene, its derivatives and their conjugates with biologically active compounds are presented. The potential use of these compounds concerns various areas of medicine, including anti-inflammatory with peptic ulcers, antineoplastic with leukemia, antidiabetes, antiretroviral with HIV-1, antimicrobial, including antimicrobial photodynamic therapy, and antifungal.

Titanium Dioxide Nanoparticles: Prospects and Applications in Medicine.

Metallic and metal oxide nanoparticles (NPs), including titanium dioxide NPs, among polymeric NPs, liposomes, micelles, quantum dots, dendrimers, or fullerenes, are becoming more and more important due to their potential use in novel medical therapies. Titanium dioxide (titanium(IV) oxide, titania, TiO2) is an inorganic compound that owes its recent rise in scientific interest to photoactivity. After the illumination in aqueous media with UV light, TiO2 produces an array of reactive oxygen species (ROS). The capability to produce ROS and thus induce cell death has found application in the photodynamic therapy (PDT) for the treatment of a wide range of maladies, from psoriasis to cancer. Titanium dioxide NPs were studied as photosensitizing agents in the treatment of malignant tumors as well as in photodynamic inactivation of antibiotic-resistant bacteria. Both TiO2 NPs themselves, as well as their composites and combinations with other molecules or biomolecules, can be successfully used as photosensitizers in PDT. Moreover, various organic compounds can be grafted on TiO2 nanoparticles, leading to hybrid materials. These nanostructures can reveal increased light absorption, allowing their further use in targeted therapy in medicine. In order to improve efficient anticancer and antimicrobial therapies, many approaches utilizing titanium dioxide were tested. Results of selected studies presenting the scope of potential uses are discussed in this review.

Detection of bisphenol A, cumylphenol and parabens in surface waters of Greater Poland Voivodeship.

Amounts of bisphenol A (BPA), 4-cumylphenol (CP) and 5 parabens - methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP) and benzylparaben (BzP) in Greater Poland Voivodeship's surface waters are reported. The water samples were collected from selected 15 locations in 2015-2016 at seven different time points: in March, June, August, and October 2015 and March, June, and September 2016. MP was found in every tested sample with typical concentration at several dozen nanograms per liter and the highest level almost 1600 ng L-1 in a sample collected from the Warta River in October 2015. The other four parabens were determined at considerably lower concentrations than MP at levels not exceeding 100 ng L-1 with PP found at the highest and BzP at the lowest levels. BPA was determined at similar concentration level to parabens - between 5 ng L-1 and 95 ng L-1 and CP was found only in a limited number of samples. Noticeable seasonal changes of paraben concentrations were found showing that for these compounds the pollutant release factor dominates both the biodegradation factor and the water volume factor. These seasonal changes were not observed for BPA and CP. Out of all determined parabens only MP was found at considerably higher concentrations than BPA. However, MP's endocrine properties are much lower than those of BPA posing a lower environmental impact potential than BPA. Influence of other (more endocrine disrupting) parabens is also relatively weak in comparison to BPA due to their considerably lower concentrations in the environment.